Ischemia-reperfusion promotes hepatic cancer growth and expression of VEGF and MMP-9 in adjacent tissues of cancer in nude mice
Journal Title: Di-er Junyi Daxue Xuebao - Year 2008, Vol 29, Issue 5
Abstract
Objective：To observe the influence of ischemia-reperfusion (I/R) on hepatoma growth and on the expression of genes associated with tumor metastasis and recurrence (VEGF and MMP-9) in the adjacent tissues of cancer in nude mice. Methods: BALB/c nude mouse model bearing Hep3B-tumor in the liver was established and the model mice were evenly randomly into 5 groups: sham group and ischemia/reperfusion 1 h, 6 h, 5 d, and 7 d groups (n=8). I/R models were established by blocking porta hepatic; the sham group underwent the same treatment as the I/R model group except for blocking of porta hepatic. ALT and AST were detected in I/R 1 h and 6 h groups. Real-time-PCR was employed to detect the change of VEGF and MMP-9 in the adjacent tissues of cancer and the results were compared with that of the control group (n=6). Histopathological changes of liver were studied by H-E staining and necrotic areas were calculated in I/R 5 d and 7 d groups(n=6). The remnant tumor bearing mice were sacrificed 2 weeks after I/R to measure the volume and mass of the tumors. Results: Two weeks later, the tumor volume and mass in I/R group were increased compared with those in the sham group ([209.6±25.74] mm3 vs [330.6±32.01] mm3,[0.214±0.036] g vs [0.374±0.045] g, P<0.01). Levels of ALT and AST were significantly elevated in I/R 1 h and 6 h groups compared with those in the sham group (P<0.01). H-E staining showed that the infiltration of inflammatory cells around the tumors and the areas of necrosis became more prominent 5 days after I/R compared with the sham operation group (P<0.05). The necrosis area was reduced 7 days after I/R compared with 5 days after I/R (P<0.05); however, the necrosis area was replaced by invasion of tumor cells (P<0.05). It was found that the expression of VEGF and MMP-9 mRNA was higher in the adjacent tissues of cancer after I/R than that in the sham group (P<0.01), and the expression of the 2 was correlated with each other (r=0.418, P<0.01). Conclusion: I/R induced by blocking porta hepatic can accelerate tumor cell growth and promote expression of VEGF and MMP-9 in the adjacent tissues of cancer.
Authors and Affiliations
Li AI, Xiao-feng ZHANG, Peng LIU, Lei CHEN, He-ping HU
Keywords
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