| Purpose:To determine the inhibitory effect of10-hydroxycamptothecin liposome on hypoxia-induced factor-la (HIF-la) in rabbit VX2cells and human HepG2cells in vitro.Materials and Methods:Rabbit VX2cells and human HepG2cells were cultured under normoxic (21%O2) and hypoxic conditions respectively (1%O2). Both of the two kinds of cells were treated with different HCPT-lipo concentrations for16hours. Cell Counting Kit-8assay was used to determine the cell viability. Real-time PCR was performed to examine the expression of HIF-1a mRNA of the cells. Western blot analysis was used to examine the expression of HIF-1α protein.Results:There was no significant difference in cytotoxicity caused by HCPT-lipo was noted between normoxic and hypoxic in VX2cells and HepaG2cells. Hypoxia, promote expression of HIF-la protein but not happened in its mRNA. With the increasing concentrations of HCPT-lipo, the inhibition ability of the drug enhanced.Conclusions:HCPT-lipo inhibits the expression of HIF-la protein induced by hypoxia in the two kinds of tumor cells, and it occurs at post-transcriptional level. The inhibition is dose-dependent.Purpose:To evaluate expression of hypoxia-inducible factor-la in animal models of liver tumors after transcatheter arterial embolization, and the correlation of hypoxia-inducible factor-la with angiogenesis, drug resistance, and metastasis.Materials and Methods:Twenty rabbit’s implanted VX2liver tumors were established. The experimental group(n=10) were treated by transcatheter hepatic arterial embolization(TAE) with polyvinyl alcohol(PVA) particles sized150～250μm; The control group were treated underwent sham embolization with normal saline. Six hours and3days treatment, animals were sacrificed, and samples were harvested. Expression of HIF-la, VEGF, and G-gp and MMP-2proteins was examined immunohistochemically. Real-time PCR was used to examine the HIF-la, VEGF, MDR1, MMP-2mRNA levels.Results:The animal models were established successfully, the sizes of tumors were detected by MR (P=0.524). The lever of HIF-la protein was significantly higher in experimental group than that in control group(P=0.001).So as the expression of mRNA of VEGF、MDR1、MMP-2(P=0.00、P=0.00、P=0.00,respectively). And HIF-1α protein level was significantly correlated with levels of mRNA and proteins of VEGF、MDR1、MMP-2(r=0.635, P=0.001、 r=0.773,P=0.00、r=0.758, P=0.012respectively)Conclusions:After TAE the tumor hypoxia becomes worse, the residual cells experience and induce the expression of HIF-1α, and HIF-1α generates a overexpression of VEGF、MDR1、MMP-2, which allow the tumors to survive and even evolve.Purpose:To study the inhibitory effect of transcatheter hepatic artery administration of10-hydroxycamptothecin liposome on tumor hypoxia response in animal models after transcatheter arterial embolization.Materials and Methods:Forty rabbits with implanted VX2liver tumor were randomly divided into4groups with10of each. After a microcatheter was placed into the hepatic artery, the treatments were performed by injecting HCPT-lipo mixed lipiodol PVA particles (group A), PVA (group B), HCPT-lipo (group C) and normal saline (group D), respectively. Six hours or3days after the injection, animals were sacrificed. The mRNA levels of HIF-1α, VEGF、MDR1and MMP-2was detected by TR-PCR. Immunohistochemical staining was used to show the protein levels of HIF-1α, VEGF、MDR1and MMP-2.Results:The levels of HIF-1α and VEGF, MMP-2, G-gp in tumors of group B were significantly higher than those of group A, C and D (P<0.05). There was no significant differences were noted among group A, C and D (P>0.05). The protein level of HIF-la was significantly correlated with that of VEGF、MMP-2、G-gp(r=0.816,r=0.655,r=0.677,respectively)Conclusion:Transcatheter infusion of HCPT-lipo has inhibitory effect on HIF-1α expression and angiogenesis, multidrug resistant, invasion and metastasis in liver tumors after transcatheter arterial embolization. |
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