Research progress of vitamin D in the development and progression of hepatocellular carcinoma and its clinical transformation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DING Dongyang , SUN Dapeng ,  YUAN Shengxian ,  ZHOU Weiping

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, P. R. China;

Corresponding author：

YUAN Shengxian, Email: yuanshengx@126.com; ZHOU Weiping, Email: ehphwp3@163.com

Keywords：

hepatocellular carcinoma; vitamin D; vitamin D receptor; clinical transformation and application; prognostic indicator; review

DOI：

10.7507/1007-9424.202008032

Video：

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Objective To summarize the current research progress of the relationship between vitamin D and the development and progression of hepatocellular carcinoma (HCC), and relevant clinical translational application researches.Methods The related literatures at home and abroad were searched to review the studies on the synthesis and metabolism of vitamin D, classic and non-classical effects of vitamin D, and the relationship between vitamin D and the development and progression of HCC, as well as relevant clinical translational application.Results Vitamin D was an important cytokine that regulated the body’s mineral and bone metabolism, and its anti-proliferation, pro-differentiation, pro-apoptosis, anti-inflammation, immune regulation, and other non-classical effects, had received more and more attentions in recent years. The existing studies had found that vitamin D was closely associated with HCC, which affected the development and progression of HCC through various mechanisms. Epidemiology showed that vitamin D levels were closely related to the prognosis of HCC patients. Whether vitamin D could be used as a clinical prognostic indicator and treatment plan for HCC still needed further clinical evidence to confirm.Conclusion Vitamin D plays an important role in the regulation of the development and progression of HCC, and exploration of the association between vitamin D and HCC and related clinical translation problems are expected to provide a new approach for the prevention and treatment of HCC.

Citation： DING Dongyang, SUN Dapeng, YUAN Shengxian, ZHOU Weiping. Research progress of vitamin D in the development and progression of hepatocellular carcinoma and its clinical transformation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(5): 688-694. doi: 10.7507/1007-9424.202008032 Copy

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2.	吴孟超, 吴东. 原发性肝癌综合治疗的现状与展望. 癌症进展, 2005, 3(5): 410-412, 422.
3.	Giannini EG, Farinati F, Ciccarese F, et al. Prognosis of untreated hepatocellular carcinoma. Hepatology, 2015, 61(1): 184-190.
4.	European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol, 2012, 56(4): 908-943.
5.	Kim TH, Yun SG, Choi J, et al. Differential impact of serum25-hydroxyvitamin D3 levels on the prognosis of patients with liver cirrhosis according to MELD and Child-Pugh scores. J Korean Med Sci, 2020, 35(19): e129.
6.	Ravid A, Rapaport N, Issachar A, et al. 25-hydroxyvitamin D inhibits hepatitis C virus production in hepatocellular carcinoma cell line by a vitamin D receptor-independent mechanism. Int J Mol Sci, 2019, 20(9): 2367.
7.	Hoan NX, Khuyen N, Binh MT, et al. Association of vitamin D deficiency with hepatitis B virus - related liver diseases. BMC Infect Dis, 2016, 16(1): 507.
8.	Bouillon R, Suda T. Vitamin D: calcium and bone homeostasis during evolution. Bonekey Rep, 2014, 3: 480.
9.	Díaz L, Díaz-Muñoz M, García-Gaytán AC, et al. Mechanistic effects of calcitriol in cancer biology. Nutrients, 2015, 7(6): 5020-5050.
10.	MacLaughlin JA, Anderson RR, Holick MF. Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. Science, 1982, 216(4549): 1001-1003.
11.	Cheng JB, Levine MA, Bell NH, et al. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A, 2004, 101(20): 7711-7715.
12.	Schuster I. Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta, 2011, 1814(1): 186-199.
13.	Jones G, Schnoes HK, DeLuca HF. Isolation and identification of1, 25-dihydroxyvitamin D2. Biochemistry, 1975, 14(6): 1250-1256.
14.	Deluca HF. History of the discovery of vitamin D and its active metabolites. Bonekey Rep, 2014, 3: 479.
15.	Bakke D, Sun J. Ancient nuclear receptor VDR with new functions: microbiome and inflammation. Inflamm Bowel Dis, 2018, 24(6): 1149-1154.
16.	Ramagopalan SV, Heger A, Berlanga AJ, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res, 2010, 20(10): 1352-1360.
17.	Muralidhar S, Filia A, Nsengimana J, et al. Vitamin D-VDR signaling inhibits Wnt/β-catenin-mediated melanoma progression and promotes antitumor immunity. Cancer Res, 2019, 79(23): 5986-5998.
18.	Stumpf WE, Sar M, Reid FA, et al. Target cells for 1, 25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science, 1979, 206(4423): 1188-1190.
19.	Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab, 2010, 95(2): 471-478.
20.	Walters MR. Newly identified actions of the vitamin D endocrine system. Endocr Rev, 1992, 13(4): 719-764.
21.	Campbell MJ, Trump DL. Vitamin D receptor signaling and cancer. Endocrinol Metab Clin North Am, 2017, 46(4): 1009-1038.
22.	Watkins RR, Lemonovich TL, Salata RA. An update on the association of vitamin D deficiency with common infectious diseases. Can J Physiol Pharmacol, 2015, 93(5): 363-368.
23.	Sadeghi K, Wessner B, Laggner U, et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol, 2006, 36(2): 361-370.
24.	Trochoutsou AI, Kloukina V, Samitas K, et al. Vitamin-D in the immune system: genomic and non-genomic actions. Mini Rev Med Chem, 2015, 15(11): 953-963.
25.	Goncalves-Mendes N, Talvas J, Dualé C, et al. Impact of vitamin D supplementation on influenza vaccine response and immune functions in deficient elderly persons: a randomized placebo-controlled trial. Front Immunol, 2019, 10: 65.
26.	Chen S, Sims GP, Chen XX, et al. Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol, 2007, 179(3): 1634-1647.
27.	Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl Med, 2016, 8(328): 328rv4.
28.	Dimitrov V, Bouttier M, Boukhaled G, et al. Hormonal vitamin D up-regulates tissue-specific PD-L1 and PD-L2 surface glycoprotein expression in humans but not mice. J Biol Chem, 2017, 292(50): 20657-20668.
29.	Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology, 2006, 147(12): 5542-5548.
30.	Lösel R, Wehling M. Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol, 2003, 4(1): 46-56.
31.	Shah S, Islam MN, Dakshanamurthy S, et al. The molecular basis of vitamin D receptor and beta-catenin crossregulation. Mol Cell, 2006, 21(6): 799-809.
32.	Skaaby T, Husemoen LL, Borglykke A, et al. Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine, 2014, 47(1): 213-220.
33.	Finkelmeier F, Kronenberger B, Köberle V, et al. Severe25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma - a prospective cohort study. Aliment Pharmacol Ther, 2014, 39(10): 1204-1212.
34.	Fedirko V, Duarte-Salles T, Bamia C, et al. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study. Hepatology, 2014, 60(4): 1222-1230.
35.	Buonomo AR, Scotto R, Zappulo E, et al. Severe vitamin D deficiency increases mortality among patients with liver cirrhosis regardless of the presence of HCC. In Vivo, 2019, 33(1): 177-182.
36.	Hammad LN, Abdelraouf SM, Hassanein FS, et al. CirculatingIL-6, IL-17 and vitamin D in hepatocellular carcinoma: potential biomarkers for a more favorable prognosis? J Immunotoxicol, 2013, 10(4): 380-386.
37.	Fang AP, Long JA, Zhang YJ, et al. Serum bioavailable, rather than total, 25-hydroxyvitamin D levels are associated with hepatocellular carcinoma survival. Hepatology, 2020, 72(1): 169-182.
38.	Wu YQ, Fan WZ, Xue M, et al. 25-OH-vitamin D deficiency identifies poor tumor response in hepatocellular carcinoma treated with transarterial chemoembolization. Clin Transl Oncol, 2020, 22(1): 70-80.
39.	Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, 2006, 311(5768): 1770-1773.
40.	Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int, 2006, 26(10): 1175-1186.
41.	Duran A, Hernandez ED, Reina-Campos M, et al. p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis, and liver cancer. Cancer Cell, 2016, 30(4): 595-609.
42.	Ding N, Yu RT, Subramaniam N, et al. A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell, 2013, 153(3): 601-613.
43.	Artaza JN, Norris KC. Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells. J Endocrinol, 2009, 200(2): 207-221.
44.	Caputo A, Pourgholami MH, Akhter J, et al. 1, 25-dihydroxyvitamin D(3) induced cell cycle arrest in the human primary liver cancer cell line HepG2. Hepatol Res, 2003, 26(1): 34-39.
45.	Tadesse S, Caldon EC, Tilley W, et al. Cyclin-dependent kinase 2 inhibitors in cancer therapy: an update. J Med Chem, 2019, 62(9): 4233-4251.
46.	Hager G, Formanek M, Gedlicka C, et al. 1, 25(OH)2 vitamin D3 induces elevated expression of the cell cycle-regulating genes P21 and P27 in squamous carcinoma cell lines of the head and neck. Acta Otolaryngol, 2001, 121(1): 103-109.
47.	Liu Y, Wang M, Xu W, et al. Active vitamin D supplementation alleviates initiation and progression of nonalcoholic fatty liver disease by repressing the p53 pathway. Life Sci, 2020, 241: 117086.
48.	Huang J, Yang G, Huang Y, et al. 1, 25(OH)2D3 inhibits the progression of hepatocellular carcinoma via downregulating HDAC2 and upregulating P21(WAFI/CIP1). Mol Med Rep, 2016, 13(2): 1373-1380.
49.	Zhou J, Yu Q, Chng WJ. TXNIP (VDUP-1, TBP-2): a major redox regulator commonly suppressed in cancer by epigenetic mechanisms. Int J Biochem Cell Biol, 2011, 43(12): 1668-1673.
50.	Hamilton JP, Potter JJ, Koganti L, et al. Effects of vitamin D3 stimulation of thioredoxin-interacting protein in hepatocellular carcinoma. Hepatol Res, 2014, 44(13): 1357-1366.
51.	Rizvi A, Farhan M, Naseem I, et al. Calcitriol-copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma. Apoptosis, 2016, 21(9): 997-1007.
52.	Chen J, Katz LH, Muñoz NM, et al. Vitamin D deficiency promotes liver tumor growth in transforming growth factor-β/Smad3-deficient mice through Wnt and Toll-like receptor 7 pathway modulation. Sci Rep, 2016, 6: 30217.
53.	Matsuda A, Ishiguro K, Yan IK, et al. Therapeutic efficacy of vitamin d in experimental c-MET-β-catenin-driven hepatocellular cancer. Gene Expr, 2019, 19(2): 151-159.
54.	Falleti E, Bitetto D, Fabris C, et al. Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis. World J Gastroenterol, 2010, 16(24): 3016-3024.
55.	Hung CH, Chiu YC, Hu TH, et al. Significance of vitamin d receptor gene polymorphisms for risk of hepatocellular carcinoma in chronic hepatitis C. Transl Oncol, 2014, 7(4): 503-507.
56.	Peng Q, Yang S, Lao X, et al. Association of single nucleotide polymorphisms in VDR and DBP genes with HBV-related hepatocellular carcinoma risk in a Chinese population. PLoS One, 2014, 9(12): e116026.
57.	Quan Y, Yang J, Qin T, et al. Associations between twelve common gene polymorphisms and susceptibility to hepatocellular carcinoma: evidence from a meta-analysis. World J Surg Oncol, 2019, 17(1): 216.
58.	Chiang KC, Persons KS, Istfan NW, et al. Fish oil enhances the antiproliferative effect of 1alpha, 25-dihydroxyvitamin D3 on liver cancer cells. Anticancer Res, 2009, 29(9): 3591-3596.
59.	Chiang KC, Yen CL, Yeh CN, et al. Hepatocellular carcinoma cells express 25(OH)D-1α-hydroxylase and are able to convert 25(OH)D to 1α, 25(OH)2D, leading to the 25(OH)D-induced growth inhibition. J Steroid Biochem Mol Biol, 2015, 154: 47-52.
60.	Finlay IG, Stewart GJ, Ahkter J, et al. A phase one study of the hepatic arterial administration of 1, 25-dihydroxyvitamin D3 for liver cancers. J Gastroenterol Hepatol, 2001, 16(3): 333-337.
61.	Morris DL, Jourdan JL, Finlay I, et al. Hepatic intra-arterial injection of 1, 25-dihydroxyvitamin D3 in lipiodol: pilot study in patients with hepatocellular carcinoma. Int J Oncol, 2002, 21(4): 901-906.
62.	Leyssens C, Verlinden L, Verstuyf A. Antineoplastic effects of1, 25(OH)2D3 and its analogs in breast, prostate and colorectal cancer. Endocr Relat Cancer, 2013, 20(2): R31-R47.
63.	Chiang KC, Yeh CN, Chen HY, et al. 19-Nor-2α-(3-hydroxypropyl)-1α, 25-dihydroxyvitamin D3 (MART-10) is a potent cell growth regulator with enhanced chemotherapeutic potency in liver cancer cells. Steroids, 2011, 76(13): 1513-1519.
64.	Ghous Z, Akhter J, Pourgholami MH, et al. Inhibition of hepatocellular cancer by EB1089: in vitro and in vive study. Anticancer Res, 2008, 28(6A): 3757-3761.
65.	Sahpazidou D, Stravoravdi P, Toliou T, et al. Significant experimental decrease of the hepatocellular carcinoma incidence in C3H/Sy mice after long-term administration of EB1089, a vitamin D analogue. Oncol Res, 2003, 13(5): 261-268.
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1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin, 2017, 67(1): 7-30.
2. 吴孟超, 吴东. 原发性肝癌综合治疗的现状与展望. 癌症进展, 2005, 3(5): 410-412, 422.
3. Giannini EG, Farinati F, Ciccarese F, et al. Prognosis of untreated hepatocellular carcinoma. Hepatology, 2015, 61(1): 184-190.
4. European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol, 2012, 56(4): 908-943.
5. Kim TH, Yun SG, Choi J, et al. Differential impact of serum25-hydroxyvitamin D3 levels on the prognosis of patients with liver cirrhosis according to MELD and Child-Pugh scores. J Korean Med Sci, 2020, 35(19): e129.
6. Ravid A, Rapaport N, Issachar A, et al. 25-hydroxyvitamin D inhibits hepatitis C virus production in hepatocellular carcinoma cell line by a vitamin D receptor-independent mechanism. Int J Mol Sci, 2019, 20(9): 2367.
7. Hoan NX, Khuyen N, Binh MT, et al. Association of vitamin D deficiency with hepatitis B virus - related liver diseases. BMC Infect Dis, 2016, 16(1): 507.
8. Bouillon R, Suda T. Vitamin D: calcium and bone homeostasis during evolution. Bonekey Rep, 2014, 3: 480.
9. Díaz L, Díaz-Muñoz M, García-Gaytán AC, et al. Mechanistic effects of calcitriol in cancer biology. Nutrients, 2015, 7(6): 5020-5050.
10. MacLaughlin JA, Anderson RR, Holick MF. Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. Science, 1982, 216(4549): 1001-1003.
11. Cheng JB, Levine MA, Bell NH, et al. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A, 2004, 101(20): 7711-7715.
12. Schuster I. Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta, 2011, 1814(1): 186-199.
13. Jones G, Schnoes HK, DeLuca HF. Isolation and identification of1, 25-dihydroxyvitamin D2. Biochemistry, 1975, 14(6): 1250-1256.
14. Deluca HF. History of the discovery of vitamin D and its active metabolites. Bonekey Rep, 2014, 3: 479.
15. Bakke D, Sun J. Ancient nuclear receptor VDR with new functions: microbiome and inflammation. Inflamm Bowel Dis, 2018, 24(6): 1149-1154.
16. Ramagopalan SV, Heger A, Berlanga AJ, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res, 2010, 20(10): 1352-1360.
17. Muralidhar S, Filia A, Nsengimana J, et al. Vitamin D-VDR signaling inhibits Wnt/β-catenin-mediated melanoma progression and promotes antitumor immunity. Cancer Res, 2019, 79(23): 5986-5998.
18. Stumpf WE, Sar M, Reid FA, et al. Target cells for 1, 25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science, 1979, 206(4423): 1188-1190.
19. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab, 2010, 95(2): 471-478.
20. Walters MR. Newly identified actions of the vitamin D endocrine system. Endocr Rev, 1992, 13(4): 719-764.
21. Campbell MJ, Trump DL. Vitamin D receptor signaling and cancer. Endocrinol Metab Clin North Am, 2017, 46(4): 1009-1038.
22. Watkins RR, Lemonovich TL, Salata RA. An update on the association of vitamin D deficiency with common infectious diseases. Can J Physiol Pharmacol, 2015, 93(5): 363-368.
23. Sadeghi K, Wessner B, Laggner U, et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol, 2006, 36(2): 361-370.
24. Trochoutsou AI, Kloukina V, Samitas K, et al. Vitamin-D in the immune system: genomic and non-genomic actions. Mini Rev Med Chem, 2015, 15(11): 953-963.
25. Goncalves-Mendes N, Talvas J, Dualé C, et al. Impact of vitamin D supplementation on influenza vaccine response and immune functions in deficient elderly persons: a randomized placebo-controlled trial. Front Immunol, 2019, 10: 65.
26. Chen S, Sims GP, Chen XX, et al. Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol, 2007, 179(3): 1634-1647.
27. Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl Med, 2016, 8(328): 328rv4.
28. Dimitrov V, Bouttier M, Boukhaled G, et al. Hormonal vitamin D up-regulates tissue-specific PD-L1 and PD-L2 surface glycoprotein expression in humans but not mice. J Biol Chem, 2017, 292(50): 20657-20668.
29. Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology, 2006, 147(12): 5542-5548.
30. Lösel R, Wehling M. Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol, 2003, 4(1): 46-56.
31. Shah S, Islam MN, Dakshanamurthy S, et al. The molecular basis of vitamin D receptor and beta-catenin crossregulation. Mol Cell, 2006, 21(6): 799-809.
32. Skaaby T, Husemoen LL, Borglykke A, et al. Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine, 2014, 47(1): 213-220.
33. Finkelmeier F, Kronenberger B, Köberle V, et al. Severe25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma - a prospective cohort study. Aliment Pharmacol Ther, 2014, 39(10): 1204-1212.
34. Fedirko V, Duarte-Salles T, Bamia C, et al. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study. Hepatology, 2014, 60(4): 1222-1230.
35. Buonomo AR, Scotto R, Zappulo E, et al. Severe vitamin D deficiency increases mortality among patients with liver cirrhosis regardless of the presence of HCC. In Vivo, 2019, 33(1): 177-182.
36. Hammad LN, Abdelraouf SM, Hassanein FS, et al. CirculatingIL-6, IL-17 and vitamin D in hepatocellular carcinoma: potential biomarkers for a more favorable prognosis? J Immunotoxicol, 2013, 10(4): 380-386.
37. Fang AP, Long JA, Zhang YJ, et al. Serum bioavailable, rather than total, 25-hydroxyvitamin D levels are associated with hepatocellular carcinoma survival. Hepatology, 2020, 72(1): 169-182.
38. Wu YQ, Fan WZ, Xue M, et al. 25-OH-vitamin D deficiency identifies poor tumor response in hepatocellular carcinoma treated with transarterial chemoembolization. Clin Transl Oncol, 2020, 22(1): 70-80.
39. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, 2006, 311(5768): 1770-1773.
40. Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int, 2006, 26(10): 1175-1186.
41. Duran A, Hernandez ED, Reina-Campos M, et al. p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis, and liver cancer. Cancer Cell, 2016, 30(4): 595-609.
42. Ding N, Yu RT, Subramaniam N, et al. A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell, 2013, 153(3): 601-613.
43. Artaza JN, Norris KC. Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells. J Endocrinol, 2009, 200(2): 207-221.
44. Caputo A, Pourgholami MH, Akhter J, et al. 1, 25-dihydroxyvitamin D(3) induced cell cycle arrest in the human primary liver cancer cell line HepG2. Hepatol Res, 2003, 26(1): 34-39.
45. Tadesse S, Caldon EC, Tilley W, et al. Cyclin-dependent kinase 2 inhibitors in cancer therapy: an update. J Med Chem, 2019, 62(9): 4233-4251.
46. Hager G, Formanek M, Gedlicka C, et al. 1, 25(OH)2 vitamin D3 induces elevated expression of the cell cycle-regulating genes P21 and P27 in squamous carcinoma cell lines of the head and neck. Acta Otolaryngol, 2001, 121(1): 103-109.
47. Liu Y, Wang M, Xu W, et al. Active vitamin D supplementation alleviates initiation and progression of nonalcoholic fatty liver disease by repressing the p53 pathway. Life Sci, 2020, 241: 117086.
48. Huang J, Yang G, Huang Y, et al. 1, 25(OH)2D3 inhibits the progression of hepatocellular carcinoma via downregulating HDAC2 and upregulating P21(WAFI/CIP1). Mol Med Rep, 2016, 13(2): 1373-1380.
49. Zhou J, Yu Q, Chng WJ. TXNIP (VDUP-1, TBP-2): a major redox regulator commonly suppressed in cancer by epigenetic mechanisms. Int J Biochem Cell Biol, 2011, 43(12): 1668-1673.
50. Hamilton JP, Potter JJ, Koganti L, et al. Effects of vitamin D3 stimulation of thioredoxin-interacting protein in hepatocellular carcinoma. Hepatol Res, 2014, 44(13): 1357-1366.
51. Rizvi A, Farhan M, Naseem I, et al. Calcitriol-copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma. Apoptosis, 2016, 21(9): 997-1007.
52. Chen J, Katz LH, Muñoz NM, et al. Vitamin D deficiency promotes liver tumor growth in transforming growth factor-β/Smad3-deficient mice through Wnt and Toll-like receptor 7 pathway modulation. Sci Rep, 2016, 6: 30217.
53. Matsuda A, Ishiguro K, Yan IK, et al. Therapeutic efficacy of vitamin d in experimental c-MET-β-catenin-driven hepatocellular cancer. Gene Expr, 2019, 19(2): 151-159.
54. Falleti E, Bitetto D, Fabris C, et al. Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis. World J Gastroenterol, 2010, 16(24): 3016-3024.
55. Hung CH, Chiu YC, Hu TH, et al. Significance of vitamin d receptor gene polymorphisms for risk of hepatocellular carcinoma in chronic hepatitis C. Transl Oncol, 2014, 7(4): 503-507.
56. Peng Q, Yang S, Lao X, et al. Association of single nucleotide polymorphisms in VDR and DBP genes with HBV-related hepatocellular carcinoma risk in a Chinese population. PLoS One, 2014, 9(12): e116026.
57. Quan Y, Yang J, Qin T, et al. Associations between twelve common gene polymorphisms and susceptibility to hepatocellular carcinoma: evidence from a meta-analysis. World J Surg Oncol, 2019, 17(1): 216.
58. Chiang KC, Persons KS, Istfan NW, et al. Fish oil enhances the antiproliferative effect of 1alpha, 25-dihydroxyvitamin D3 on liver cancer cells. Anticancer Res, 2009, 29(9): 3591-3596.
59. Chiang KC, Yen CL, Yeh CN, et al. Hepatocellular carcinoma cells express 25(OH)D-1α-hydroxylase and are able to convert 25(OH)D to 1α, 25(OH)2D, leading to the 25(OH)D-induced growth inhibition. J Steroid Biochem Mol Biol, 2015, 154: 47-52.
60. Finlay IG, Stewart GJ, Ahkter J, et al. A phase one study of the hepatic arterial administration of 1, 25-dihydroxyvitamin D3 for liver cancers. J Gastroenterol Hepatol, 2001, 16(3): 333-337.
61. Morris DL, Jourdan JL, Finlay I, et al. Hepatic intra-arterial injection of 1, 25-dihydroxyvitamin D3 in lipiodol: pilot study in patients with hepatocellular carcinoma. Int J Oncol, 2002, 21(4): 901-906.
62. Leyssens C, Verlinden L, Verstuyf A. Antineoplastic effects of1, 25(OH)2D3 and its analogs in breast, prostate and colorectal cancer. Endocr Relat Cancer, 2013, 20(2): R31-R47.
63. Chiang KC, Yeh CN, Chen HY, et al. 19-Nor-2α-(3-hydroxypropyl)-1α, 25-dihydroxyvitamin D3 (MART-10) is a potent cell growth regulator with enhanced chemotherapeutic potency in liver cancer cells. Steroids, 2011, 76(13): 1513-1519.
64. Ghous Z, Akhter J, Pourgholami MH, et al. Inhibition of hepatocellular cancer by EB1089: in vitro and in vive study. Anticancer Res, 2008, 28(6A): 3757-3761.
65. Sahpazidou D, Stravoravdi P, Toliou T, et al. Significant experimental decrease of the hepatocellular carcinoma incidence in C3H/Sy mice after long-term administration of EB1089, a vitamin D analogue. Oncol Res, 2003, 13(5): 261-268.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress of vitamin D in the development and progression of hepatocellular carcinoma and its clinical transformation

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