Effects of Recombinant Adenovirus-Mediated Overexpression of hTIMP-1 on Proliferation of Human Liver Cancer Cell Line HepG2 in Vitro_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XIA Dong ¹ , XU Liang ² , WAN Liyi ² , WANG Yuanzheng ² , ZUO Huaiquan ¹ , YAN Lnan ¹

Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Tissue inhibitor of metalloproteinase; Hepatocellular carcinoma; Adenovirus; Gene therapy

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Objective　 To explore the effects of overexpression of human tissue inhibitors of metalloproteinase-1 (hTIMP-1) on proliferation of human liver cancer cell line HepG2 in vitro.
Methods　 A recombinant adenoviral vector containing full-length cDNA of hTIMP-1 was generated and transfected into HepG2. The viral titer was checked by measuring GFP, and the expression of hTIMP-1 in vitro was detected by the techniques of Western blot and semi-quantitative RT-PCR. The ultrastructure was observed by transmission electron microscope and the effects of overexpression of hTIMP-1 on proliferation of HepG2 in vitro was analyzed by MTT assay and growth curve.
Results 　The resultant AdhTIMP-1 was successfully constructed and the expression of hTIMP-1 was detected by Western blot and RT-PCR. The growth and proliferation of HepG2, which had been transfected with AdhTIMP-1,　 was significantly inhibited.
Conclusion 　The proliferation of HepG2 was markedly inhibited by recombinant adenovirus-mediated overexpression of hTIMP-1, which may pave the way for further application in liver gene therapy.

Citation： XIA Dong,XU Liang,WAN Liyi,WANG Yuanzheng,ZUO Huaiquan,YAN Lnan. Effects of Recombinant Adenovirus-Mediated Overexpression of hTIMP-1 on Proliferation of Human Liver Cancer Cell Line HepG2 in Vitro. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(4): 409-412. doi: Copy

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2.	He TC, Zhou S, da Costa LT, et al. A simplified system for generating recombinant adenovirus [Ｊ]　. Proc Natl Acad Sci USA, 1998; 95(12)∶2509.
3.	Xia D, Yan LN, Tong Y, et al. Construction of recombinant adenoviral vector carrying human tissue inhibitor of metalloproteinase-1 gene and its expression in vitro [Ｊ]　. Hepat Pancrea Dis International, 2005; 4(2)∶259.
4.	Matsumoto E, Nakatsukasa H, Nouso K, et al. Increased levels of tissue inhibitor of metalloproteinase-1 in human hepatocellular carcinoma [Ｊ]　. Liver Int, 2004; 24(4)∶379.
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6.	Xia D, Zhang MM, Yan LN. Recent advances in liver-directed gene transfer vectors [Ｊ]　. Hepat Pancrea Dis International, 2004; 3(3)∶332.
7.	Tran PL, Vigneron JP, Pericat D, et al. Gene therapy for hepatocellular carcinoma using non-viral vectors composed of bis guanidinium-tren-cholesterol and plasmids encoding the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-3 [Ｊ]　. Cancer Gene Ther, 2003; 10（6）∶435.
8.	Kim JR, Kim CH. Association of a high activity of matrix metalloproteinase-9 to low levels of tissue inhibitors of metalloproteinase-1 and -3 in human hepatitis B-viral hepatoma cells [Ｊ]　. Int J Biochem Cell Biol, 2004; 36（4）∶2293.
9.	Ogasawara S, Yano H, Momosaki S, et al. Expression of matrix metalloproteinases (MMPs) in cultured epatocellular carcinoma (HCC) cells and surgically resected HCC tissues [Ｊ]　. Oncol Rep, 2005; 13（6）∶1043.
10.	Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression [Ｊ]　. Nat Rev Cancer, 2002; 2（3）∶163　.
11.	Jiang YF, Goldberg ID, Shi YE. Complex roles of tissue inhibitors of metalloproteinase in cancer [Ｊ]　. Oncogene, 2002; 21（14）∶2245.
12.	Li H, Lindenmeyer F, Grenet C, et al. AdTIMP-2 inhibits tumor growth, angiogenesis, and metastasis, and prolongs survival in mice [Ｊ]　. Hum Gene Ther, 2001; 12(5)∶515.

1. 　夏冬，严律南． MMPs-TIMPs与肝癌转移 [Ｊ]　. 中华肝胆外科杂志， 2005; 11(8)∶574.
2. 　He TC, Zhou S, da Costa LT, et al. A simplified system for generating recombinant adenovirus [Ｊ]　. Proc Natl Acad Sci USA, 1998; 95(12)∶2509.
3. 　Xia D, Yan LN, Tong Y, et al. Construction of recombinant adenoviral vector carrying human tissue inhibitor of metalloproteinase-1 gene and its expression in vitro [Ｊ]　. Hepat Pancrea Dis International, 2005; 4(2)∶259.
4. 　Matsumoto E, Nakatsukasa H, Nouso K, et al. Increased levels of tissue inhibitor of metalloproteinase-1 in human hepatocellular carcinoma [Ｊ]　. Liver Int, 2004; 24(4)∶379.
5. 　Rigg AS, Lemoine NR. Adenoviral delivery of TIMP-1 or TI-MP-2 can modify the invasive behavior of pancreatic cancer and can have a significant antitumor effect in vitro [Ｊ]　. Cancer Gene Ther, 2001; 8(3)∶869.
6. 　Xia D, Zhang MM, Yan LN. Recent advances in liver-directed gene transfer vectors [Ｊ]　. Hepat Pancrea Dis International, 2004; 3(3)∶332.
7. 　Tran PL, Vigneron JP, Pericat D, et al. Gene therapy for hepatocellular carcinoma using non-viral vectors composed of bis guanidinium-tren-cholesterol and plasmids encoding the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-3 [Ｊ]　. Cancer Gene Ther, 2003; 10（6）∶435.
8. 　Kim JR, Kim CH. Association of a high activity of matrix metalloproteinase-9 to low levels of tissue inhibitors of metalloproteinase-1 and -3 in human hepatitis B-viral hepatoma cells [Ｊ]　. Int J Biochem Cell Biol, 2004; 36（4）∶2293.
9. 　Ogasawara S, Yano H, Momosaki S, et al. Expression of matrix metalloproteinases (MMPs) in cultured epatocellular carcinoma (HCC) cells and surgically resected HCC tissues [Ｊ]　. Oncol Rep, 2005; 13（6）∶1043.
10. 　Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression [Ｊ]　. Nat Rev Cancer, 2002; 2（3）∶163　.
11. 　Jiang YF, Goldberg ID, Shi YE. Complex roles of tissue inhibitors of metalloproteinase in cancer [Ｊ]　. Oncogene, 2002; 21（14）∶2245.
12. 　Li H, Lindenmeyer F, Grenet C, et al. AdTIMP-2 inhibits tumor growth, angiogenesis, and metastasis, and prolongs survival in mice [Ｊ]　. Hum Gene Ther, 2001; 12(5)∶515.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Recombinant Adenovirus-Mediated Overexpression of hTIMP-1 on Proliferation of Human Liver Cancer Cell Line HepG2 in Vitro

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