• 1.四川大學華西醫(yī)院普外科（成都610041）;;
  • 2.四川瀘州醫(yī)學院附屬醫(yī)院普外科（瀘州646000）;

目的 　探討人基質(zhì)金屬蛋白酶組織抑制因子-1（hTIMP-1）過表達對人肝癌細胞系HepG2體外增殖的作用。
方法 　構(gòu)建攜載hTIMP-1全長cDNA的重組腺病毒載體，感染HepG2細胞，應(yīng)用Western blot及RT-PCR方法檢測TIMP-1蛋白及mRNA的表達，透射電鏡觀察細胞超微結(jié)構(gòu)改變，MTT法檢測hTIMP-1對HepG2細胞生長的影響。
結(jié)果 　成功構(gòu)建攜載hTIMP-1的重組腺病毒載體，感染HepG2細胞，實現(xiàn)其體外穩(wěn)定表達，hTIMP-1過表達對HepG2體外增殖有明顯抑制作用。
結(jié)論 　hTIMP-1過表達可抑制人肝癌細胞系HepG2的體外增殖，可用于肝癌基因治療的研究。

引用本文： 夏冬,徐亮,萬禮儀,王元正,左懷全,嚴律南. 重組腺病毒介導hTIMP-1對人肝癌細胞系體外增殖的影響. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(4): 409-412. doi: 復制

1. 　夏冬， 嚴律南． MMPs-TIMPs與肝癌轉(zhuǎn)移 [Ｊ]　. 中華肝膽外科雜志， 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.
  1. 1. 　夏冬， 嚴律南． MMPs-TIMPs與肝癌轉(zhuǎn)移 [Ｊ]　. 中華肝膽外科雜志， 2005; 11(8)∶574.
  2. 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. 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. 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. 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. 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. 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. 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. 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. 10. 　Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression [Ｊ]　. Nat Rev Cancer, 2002; 2（3）∶163　.
  11. 11. 　Jiang YF, Goldberg ID, Shi YE. Complex roles of tissue inhibitors of metalloproteinase in cancer [Ｊ]　. Oncogene, 2002; 21（14）∶2245.
  12. 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.