Effect and Mechanism of Sirtuin 1 in Invasion of Gastric Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HAOWei ¹ , CHENRui ¹ , LIURui-han ² , CHANGShuai ¹ , QIAOQiao ¹ , LIUJun-song ¹ , ZHANGZheng-liang ¹ ,  CHEXiang-ming ¹

1. Department of General Surgery, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China;
2. Card-iovascular Research Center, Medical College of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China;

Corresponding author：

CHEXiang-ming, Email: chexiang@mail.xjtu.edu.cn

Keywords：

Silent information regulator 1; Vascular endothelial growth factor A; Gastric cancer; Invasion ability

DOI：

10.7507/1007-9424.20140104

Video：

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Objective To investigate the effect and mechanism of silent information regulator 1 (SIRT1)in invasion of human gastric cancer. Methods The expressions of SIRT1 protein and vascular endothelial growth factor A (VEGF-A) protein in 46 cases of gastric cancer were tested by immunohistochemical SP method; the effect of expressions of SRIT1 and VEGF-A protein on prognosis of gastric cancer was analyzed by Kaplan-Meier test; the expressions of SRIT1 and VEGF-A protein in human gastric mucosa GES-1 cells and SGC7901 cells were tested by Western blot method; after the interference of siRNA on SIRT1 gene, expressions of SRIT1 and VEGF-A protein were also tested by Western method, and the invasion ability was determined by Transwell test. Results Compared with normal gastric mucosa tissues, expression levels of SIRT1 and VEGF-A protein of gastric tissues were both higher (P < 0.050), and survival situation of patients with SIRT1-positive (P=0.001) or SIRT1-positive and VEGF-A-positive (P=0.006) were both bad, but there was no significant difference on the relationship between prognosis of gastric cancer and expression of VEGF-A protein (P=0.091). Expression levels of SITR1 protein (P=0.010) and VEGF-A protein (P=0.020) in GES-1 cells were both higher than those of SGC7901 cells. In siRNA positive group, expressions of SIRT1 and VEGF-A protein (P=0.010) of SGC7901 cells down-regulated, and invasion ability decreased (P=0.000). Conclusions SIRT1 gene may promote the expression of VEGF-A protein and the invasion ability of gastric cancer, it may be a therapeutic target of invasion inhibition for gastric cancer.

Citation： HAOWei, CHENRui, LIURui-han, CHANGShuai, QIAOQiao, LIUJun-song, ZHANGZheng-liang, CHEXiang-ming. Effect and Mechanism of Sirtuin 1 in Invasion of Gastric Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(4): 425-431. doi: 10.7507/1007-9424.20140104 Copy

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7.	Jang KY, Hwang SH, Kwon KS, et al. SIRT1 expression is associated with poor prognosis of diffuse large B-cell lymphoma[J]. Am J Surg Pathol, 2008, 32(10):1523-1531.
8.	Alian A, Eldor A, Falk H, et al. Viral mediated gene transfer to sprouting blood vessels during angiogenesis[J]. J Virol Methods, 2002, 105(1):1-11.
9.	Farhang Ghahremani M, Goossens S, Nittner D, et al. p53 prom-otes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway[J]. Cell Death Differ, 2013, 20(7):888-897.
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11.	Yuan A, Yu CJ, Luh KT, et al. Aberrant p53 expression correlates with expression of vascular endothelial growth factor mRNA and interleukin-8 mRNA and neoangiogenesis in non-small-cell lung cancer[J]. J Clin Oncol, 2002, 20(4):900-910.
12.	Joo YE, Sohn YH, Joo SY, et al. The role of vascular endothelial growth factor (VEGF) and p53 status for angiogenesis in gastric cancer[J]. Korean J Intern Med, 2002, 17(4):211-219.
13.	傅玉峰, 丁炯. VEGF的表达与胃癌生物学特性的实验研究[J].南京医科大学学报:自然科学版, 2006, 26(9):749-752.
14.	Knight JR, Milner J. SIRT1, metabolism and cancer[J]. Curr Opin Oncol, 2012, 24(1):68-75.
15.	Jang KY, Noh SJ, Lehwald N, et al. SIRT1 and c-Myc promote liver tumor cell survival and predict poor survival of human hepatocellular carcinomas[J]. PLoS One, 2012, 7(9):e45119.
16.	Deng CX. SIRT1, is it a tumor promoter or tumor suppressor?[J]. Int J Biol Sci, 2009, 5(2):147-152.
17.	Chen HC, Jeng YM, Yuan RH, et al. SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis[J]. Ann Surg Oncol, 2012, 19(6):2011-2019.
18.	Yuan J, Pu M, Zhang Z, et al. Histone H3-K56 acetylation is important for genomic stability in mammals[J]. Cell Cycle, 2009, 8(11):1747-1753.
19.	Yi J, Luo J. SIRT1 and p53, effect on cancer, senescence and beyond[J]. Biochim Biophys Acta, 2010, 1804(8):1684-1689.
20.	Cha EJ, Noh SJ, Kwon KS, et al. Expression of DBC1 and SIRT1 is associated with poor prognosis of gastric carcinoma[J]. Clin Cancer Res, 2009, 15(13):4453-4459.
21.	Feng AN, Zhang LH, Fan XS, et al. Expression of SIRT1 in gastric cardiac cancer and its clinicopathologic significance[J]. Int J Surg Pathol, 2011, 19(6):743-750.
22.	Yuan J, Minter-Dykhouse K, Lou Z. A c-Myc-SIRT1 feedback loop regulates cell growth and transformation[J]. J Cell Biol, 2009, 185(2):203-211.
23.	Chen WY, Wang DH, Yen RC, et al. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses[J]. Cell, 2005, 123(3):437-448.
24.	Sun P, Yu H, Zhang WQ, et al. Lentivirus-mediated siRNA targeting VEGF inhibits gastric cancer growth in vivo[J]. Oncol Rep, 2012, 28(5):1687-1692.
25.	Brunet A, Sweeney LB, Sturgill JF, et al. Stress-dependent regu-lation of FOXO transcription factors by the SIRT1 deacetylase[J]. Science, 2004, 303(5666):2011-2015.
26.	Johansson N, Ahonen M, Kähäri VM. Matrix metalloproteinases in tumor invasion[J]. Cell Mol Life Sci, 2000, 57(1):5-15.

1. Herranz D, Serrano M. SIRT1:recent lessons from mouse models[J]. Nat Rev Cancer, 2010, 10(12):819-823.
2. de Boer VC, de Goffau MC, Arts IC, et al. SIRT1 stimulation by polyphenols is affected by their stability and metabolism[J]. Mech Ageing Dev, 2006, 127(7):618-627.
3. Deppert W. SIRT1 protein levels in cancer:tuning SIRT1 to the needs of a cancer cell[J]. Cell Cycle, 2008, 7(19):2947-2948.
4. Ford J, Jiang M, Milner J. Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival[J]. Cancer Res, 2005, 65(22):10457-10463.
5. 张广, 吴俊华. SIRT1与肿瘤的研究进展[J].世界华人消化杂志, 2013, 21(1):6-12.
6. Yin L, Wang X, Luo C, et al. The value of expression of M2-PK and VEGF in patients with advanced gastric cancer[J]. Cell Biochem Biophys, 2013, 67(3):1033-1039.
7. Jang KY, Hwang SH, Kwon KS, et al. SIRT1 expression is associated with poor prognosis of diffuse large B-cell lymphoma[J]. Am J Surg Pathol, 2008, 32(10):1523-1531.
8. Alian A, Eldor A, Falk H, et al. Viral mediated gene transfer to sprouting blood vessels during angiogenesis[J]. J Virol Methods, 2002, 105(1):1-11.
9. Farhang Ghahremani M, Goossens S, Nittner D, et al. p53 prom-otes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway[J]. Cell Death Differ, 2013, 20(7):888-897.
10. Yang J, Ahmed A, Poon E, et al. Small-molecule activation of p53 blocks hypoxia-inducible factor 1alpha and vascular endoth-elial growth factor expression in vivo and leads to tumor cell apop-tosis in normoxia and hypoxia[J]. Mol Cell Biol, 2009, 29(8):2243-2253.
11. Yuan A, Yu CJ, Luh KT, et al. Aberrant p53 expression correlates with expression of vascular endothelial growth factor mRNA and interleukin-8 mRNA and neoangiogenesis in non-small-cell lung cancer[J]. J Clin Oncol, 2002, 20(4):900-910.
12. Joo YE, Sohn YH, Joo SY, et al. The role of vascular endothelial growth factor (VEGF) and p53 status for angiogenesis in gastric cancer[J]. Korean J Intern Med, 2002, 17(4):211-219.
13. 傅玉峰, 丁炯. VEGF的表达与胃癌生物学特性的实验研究[J].南京医科大学学报:自然科学版, 2006, 26(9):749-752.
14. Knight JR, Milner J. SIRT1, metabolism and cancer[J]. Curr Opin Oncol, 2012, 24(1):68-75.
15. Jang KY, Noh SJ, Lehwald N, et al. SIRT1 and c-Myc promote liver tumor cell survival and predict poor survival of human hepatocellular carcinomas[J]. PLoS One, 2012, 7(9):e45119.
16. Deng CX. SIRT1, is it a tumor promoter or tumor suppressor?[J]. Int J Biol Sci, 2009, 5(2):147-152.
17. Chen HC, Jeng YM, Yuan RH, et al. SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis[J]. Ann Surg Oncol, 2012, 19(6):2011-2019.
18. Yuan J, Pu M, Zhang Z, et al. Histone H3-K56 acetylation is important for genomic stability in mammals[J]. Cell Cycle, 2009, 8(11):1747-1753.
19. Yi J, Luo J. SIRT1 and p53, effect on cancer, senescence and beyond[J]. Biochim Biophys Acta, 2010, 1804(8):1684-1689.
20. Cha EJ, Noh SJ, Kwon KS, et al. Expression of DBC1 and SIRT1 is associated with poor prognosis of gastric carcinoma[J]. Clin Cancer Res, 2009, 15(13):4453-4459.
21. Feng AN, Zhang LH, Fan XS, et al. Expression of SIRT1 in gastric cardiac cancer and its clinicopathologic significance[J]. Int J Surg Pathol, 2011, 19(6):743-750.
22. Yuan J, Minter-Dykhouse K, Lou Z. A c-Myc-SIRT1 feedback loop regulates cell growth and transformation[J]. J Cell Biol, 2009, 185(2):203-211.
23. Chen WY, Wang DH, Yen RC, et al. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses[J]. Cell, 2005, 123(3):437-448.
24. Sun P, Yu H, Zhang WQ, et al. Lentivirus-mediated siRNA targeting VEGF inhibits gastric cancer growth in vivo[J]. Oncol Rep, 2012, 28(5):1687-1692.
25. Brunet A, Sweeney LB, Sturgill JF, et al. Stress-dependent regu-lation of FOXO transcription factors by the SIRT1 deacetylase[J]. Science, 2004, 303(5666):2011-2015.
26. Johansson N, Ahonen M, Kähäri VM. Matrix metalloproteinases in tumor invasion[J]. Cell Mol Life Sci, 2000, 57(1):5-15.

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Effect and Mechanism of Sirtuin 1 in Invasion of Gastric Cancer

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