Effects of Tumor Necrosis Factor-α on Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Expression in Hepatic Cancer Cell Line HepG2_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHU Junhua , TAO Kaixiong , WANG Guobin.

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Keywords：

Tumor necrosis factor-α Liver cancer cell Vascular endothelial growth factor Matrix metal protein enzyme-9

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【Abstract】ObjectiveTo investigate whether tumor necrosis factor-α (TNF-α) enhance the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9(MMP-9) in hepatic cancer cell line HepG2 or not.
Methods Cultured HepG2 cells were treated by TNF-α with various concentration and time. The morphological changes of HepG2 cells were studied microscopically and the proliferation of HepG2 were detected by methyl thiazolyl tetrazolium (MTT). The expression of VEGF and MMP-9 mRNA in cultured HepG2 were determined by relative quantitative reverse transcription polymerase chain reaction. The VEGF and MMP-9 protein level in supernatants and in cytoplasm were determined by enzymelinked immunosorbent assay (ELISA) and by immunocytochemical staining, respectively.
Results There was a little morphological changes in HepG2 with TNF-α treatment, but no change of cell proliferation in corresponding time. The expression of VEGF and MMP-9 mRNA was enhanced gradually with the TNF-α concentration increasing, the VEGF and MMP-9 protein level in supernatants and in cytoplasm was elevated gradually with the concentration increasing. There was a dependance on the concentration when the concentration of TNF-α was lower than or equal to 104 U/L. Furthermore, the effect of promotion was close to peak when the TNF-α concentration up to 104 U/L; but no timeeffect pattern observed.
Conclusion TNF-αJP can enhance the expression of VEGF and MMP-9 at the level of mRNA and protein in hepatic cancer cell line.

Citation： ZHU Junhua,TAO Kaixiong,WANG Guobin.. Effects of Tumor Necrosis Factor-α on Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Expression in Hepatic Cancer Cell Line HepG2. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2005, 12(4): 384-389. doi: Copy

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1. Schott RJ, Morrow LA. Growth factors and angiogenesis [Ｊ]. Cardiovasc Res, 1993； 27(7)∶ 1155.
2. Nabors LB, Suswam E, Huang Y, et al. Tumor necrosis factor alpha induces angiogenic factor upregulation in malignant glioma cells: a role for RNA stabilization and HuR [Ｊ]. Cancer Res, 2003； 63(14)∶4181.
3. Huang S, Ullrich SE, BarEli M. Regulation of tumor growth and metastasis by interleukin10: the melanoma experience [Ｊ]. J Interferon Cytokine Res, 1999； 19(7)∶697.
4. Vanderslice P, Munsch CL, Rachal E, et al. Angiogenesis induced by tumor necrosis factoragr； is mediated by alpha4 integrins [Ｊ]. Angiogenesis， 1998； 2(3)∶265.
5. Hirohashi K, Yamamoto T, Uenishi T, et al. CD44 and VEGF expression in extrahepatic metastasis of human hepatocellular carcinoma [Ｊ]. Hepatogastroenterology, 2004； 51(58)∶1121.
6. Arii S, Mise M, Harada T, et al. Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential [Ｊ]. Hepatology, 1996； 24(2)∶316.
7. Yano T, Yamasaki H. Regulation of cellular invasion and matrix metalloproteinase activity in HepG2 cell by connexin 26 transfection [Ｊ]. Mol Carcinog, 2001； 31(2)∶101.
8. 张红，侯蜀新，李碗定，等.异搏定和肿瘤坏死因子α协同抗肿瘤作用的实验研究 [Ｊ]. 中国病理生理杂志， 2001； 17(7)∶639.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Tumor Necrosis Factor-α on Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Expression in Hepatic Cancer Cell Line HepG2

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