Transplanted Hepatocellular Carcinoma of Nude Mice Treated by Adenovirus Mediated mda-7 Combined with Adriamycin_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

1.Department of Biliary and Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;;
2.Department of General Surgery, Affiliated The First People’s Hospital of Shanghai Jiaotong University, Shanghai 200080, ChinaCorresponding Author: XUE Xin-bo, E-mail: xuexinbo@163.com;

Corresponding author：

Keywords：

Melanoma differentiation-associated gene-7; Adriamycin; Hepatocellular carcinoma; Transforming growth factor-β1; Vascular endothelial growth factor; Gene therapy

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Objective 　To investigate the effects of adenovirus-mediated melanoma differentiation-associated gene-7 (mda-7)/IL-24 and/or adriamycin (ADM) on transplanted human hepatoma in nude mice and to explore a new way for hepatoma gene therapy combined with chemotherapy.
Methods 　The recombinant adenovirus vector carrying Ad.mda-7 was constructed; Ad.mda-7 and/or ADM were injected into the tumor-bearing mice. Their effects on the growth of the tumor and the survival time of the mice were observed. The expressions of VEGF and TGF-β1 were detected by an immunohistochemistry method.
Results 　Ad.mda-7 was constructed and expressed in vivo successfully. Compared with other three groups 〔control group (43.4±1.67) d, ADM group (64.2±4.14) d, Ad.mda-7 group (61.4±1.67) d〕, the mice treated with Ad.mda-7 combined with ADM had longer average survival time 〔(83.8±4.82) d, P＜0.01〕; the average size of tumor treated with Ad.mda-7 combined with ADM diminished significantly compared with that treated with ADM or Ad.mda-7 separately (P＜0.01). VEGF and TGF-β1 expressions of Ad.mda-7 group were (56.2±7.7)%, (35.2±4.5)%, respectively, and were lower than those in ADM group (VEGF: P＜0.05; TGF-β1: P＜0.01). VEGF expression of Ad.mda-7+ADM group was (37.3±5.0)%, and was significantly lower than that in other three groups (P＜0.01). TGF-β1 expression of Ad.mda-7+ADM group was (31.2±3.1)% and significantly lower than that in control group and ADM group (P＜0.01), however, there was no significant difference compared with Ad.mda-7 group (P gt;0.05).
Conclusion 　Ad.mda-7 combined with ADM has b antitumor potency and synergistic effects and suppresses the growth of human HCC xenograft in nude mice, possibly by inducing the apoptosis of hepatoma cell lines and suppressing tumor angiogenesis.

Citation： CHEN Kun,XUE Xinbo,WANG Congjun ZHENG Jianwei,YU Yuan,JI Wenwei,PENG Zhihai,WU Zaide. Transplanted Hepatocellular Carcinoma of Nude Mice Treated by Adenovirus Mediated mda-7 Combined with Adriamycin. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(9): 673-677. doi: Copy

1.	El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis [Ｊ]. Gastroenterology, 2007; 132(7)∶2557.
2.	Fisher PB. Is mda-7/IL-24 a “Magic Bullet” for cancer? [Ｊ]. Cancer Res, 2005; 65(22)∶10128.
3.	Wang CJ, Xue XB, Yi JL, et al. Melanoma differentiation-associated gene-7, MDA-7/IL-24, selectively induces growth suppression, apoptosis in human hepatocellular carcinoma cell line HepG2 by replication-incompetent adenovirus vector [Ｊ]. World J Gastroenterol, 2006; 12(11)∶1774.
4.	张明满, 李德华, 苟兴华, 等. 携反义二型基质金属蛋白酶基因的重组腺病毒的构建 [Ｊ]. 中国普外基础与临床杂志, 2004; 11(5)∶428.
5.	Yao DF, Dong ZZ, Yao M. Specific molecular markers in hepatocellular carcinoma [Ｊ]. Hepatobiliary Pancreat Dis Int, 2007; 6(3)∶241.
6.	Li Y, Tian B, Yang J, et al. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics [Ｊ]. J Cancer Res Clin Oncol, 2004; 130(8)∶460.
7.	Uslu R, Borsellino N, Frost P, et al. Chemosensitization of human prostate carcinoma cell lines to anti-fas-mediated cytotoxicity and apoptosis [Ｊ]. Clin Cancer Res, 1997; 3(6)∶963.
8.	Jiang H, Lin JJ, Su ZZ, et al. Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression [Ｊ]. Oncogene, 1995; 11(12)∶2477.
9.	Sarkar D, Lebedeva IV, Gupta P, et al. Melanoma differentiation associated gene-7 (mda-7)/IL-24: a ‘magic bullet’ for cancer therapy? [Ｊ]. Expert Opin Biol Ther, 2007; 7(5)∶577.
10.	Shanker M, Gopalan B, Patel S, et al. Vitamin E succinate in combination with mda-7 results in enhanced human ovarian tumor cell killing through modulation of extrinsic and intrinsic apoptotic pathways [Ｊ]. Cancer Lett, 2007; 254(2)∶217.
11.	Lebedeva IV, Washington I, Sarkar D, et al. Strategy for reversing resistance to a single anticancer agent in human prostate and pancreatic carcinomas [Ｊ]. Proc Natl Acad Sci USA, 2007; 104(9)∶3484.
12.	Saeki T, Mhashilkar A, Swanson X, et al. Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo [Ｊ]. Oncogene, 2002; 21(29)∶4558.
13.	Avila MA, Berasain C, Sangro B, et al. New therapies for hepatocellular carcinoma [Ｊ]. Oncogene, 2006; 25(27)∶3866.
14.	朱亚青, 陈澍周, 陈玉泉, 等. TGF-β1和TβRⅠ在胆囊癌发病及预后中的作用 [Ｊ]. 中国普外基础与临床杂志, 2007; 14(4)∶448.
15.	Benckert C, Jonas S, Cramer T, et al. Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells [Ｊ]. Cancer Res, 2003; 63(5)∶1083.

1. 　El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis [Ｊ]. Gastroenterology, 2007; 132(7)∶2557.
2. 　Fisher PB. Is mda-7/IL-24 a “Magic Bullet” for cancer? [Ｊ]. Cancer Res, 2005; 65(22)∶10128.
3. 　Wang CJ, Xue XB, Yi JL, et al. Melanoma differentiation-associated gene-7, MDA-7/IL-24, selectively induces growth suppression, apoptosis in human hepatocellular carcinoma cell line HepG2 by replication-incompetent adenovirus vector [Ｊ]. World J Gastroenterol, 2006; 12(11)∶1774.
4. 　张明满, 李德华, 苟兴华, 等. 携反义二型基质金属蛋白酶基因的重组腺病毒的构建 [Ｊ]. 中国普外基础与临床杂志, 2004; 11(5)∶428.
5. 　Yao DF, Dong ZZ, Yao M. Specific molecular markers in hepatocellular carcinoma [Ｊ]. Hepatobiliary Pancreat Dis Int, 2007; 6(3)∶241.
6. 　Li Y, Tian B, Yang J, et al. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics [Ｊ]. J Cancer Res Clin Oncol, 2004; 130(8)∶460.
7. 　Uslu R, Borsellino N, Frost P, et al. Chemosensitization of human prostate carcinoma cell lines to anti-fas-mediated cytotoxicity and apoptosis [Ｊ]. Clin Cancer Res, 1997; 3(6)∶963.
8. 　Jiang H, Lin JJ, Su ZZ, et al. Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression [Ｊ]. Oncogene, 1995; 11(12)∶2477.
9. 　Sarkar D, Lebedeva IV, Gupta P, et al. Melanoma differentiation associated gene-7 (mda-7)/IL-24: a ‘magic bullet’ for cancer therapy? [Ｊ]. Expert Opin Biol Ther, 2007; 7(5)∶577.
10. 　Shanker M, Gopalan B, Patel S, et al. Vitamin E succinate in combination with mda-7 results in enhanced human ovarian tumor cell killing through modulation of extrinsic and intrinsic apoptotic pathways [Ｊ]. Cancer Lett, 2007; 254(2)∶217.
11. 　Lebedeva IV, Washington I, Sarkar D, et al. Strategy for reversing resistance to a single anticancer agent in human prostate and pancreatic carcinomas [Ｊ]. Proc Natl Acad Sci USA, 2007; 104(9)∶3484.
12. 　Saeki T, Mhashilkar A, Swanson X, et al. Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo [Ｊ]. Oncogene, 2002; 21(29)∶4558.
13. 　Avila MA, Berasain C, Sangro B, et al. New therapies for hepatocellular carcinoma [Ｊ]. Oncogene, 2006; 25(27)∶3866.
14. 　朱亚青, 陈澍周, 陈玉泉, 等. TGF-β1和TβRⅠ在胆囊癌发病及预后中的作用 [Ｊ]. 中国普外基础与临床杂志, 2007; 14(4)∶448.
15. 　Benckert C, Jonas S, Cramer T, et al. Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells [Ｊ]. Cancer Res, 2003; 63(5)∶1083.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Transplanted Hepatocellular Carcinoma of Nude Mice Treated by Adenovirus Mediated mda-7 Combined with Adriamycin

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