Genistein抑制裸鼠肝癌移植瘤侵袭性生长

Inhibitory effects of genistein on invasive growth of xenograft hepatocellular carcinoma in nude mice

目的 研究Genistein对裸鼠肾包膜下肝癌移植瘤侵袭性生长的作用及其作用机制。方法 10只裸小鼠分成2 组,每只裸小鼠均建立双侧肾包膜下肝癌移植瘤模型,予Genistein(5 mg/ml)腹腔内注射,共15 d。观察移植瘤生长及对肾实质侵袭能力变化,行肿瘤微血管密度(MVD)的免疫组化检测及MMP2与TIMP2表达的RT PCR检测。结果 Genistein治疗组瘤体积增加(63 .32±8. 96) mm3,显著小于对照组(79 .25±6. 85) mm3,P<0 .05,抑瘤率为20 1%;MVD在Genistein组(10 .422±0 .807)显著低于对照组(22 330±5 696),P<0. 05。MMP2 表达在Genistein组(0 .296±0. 132)显著低于对照组(0. 519±0 .158),P<0 .05;TIMP2 表达两组间并无显著差异,但MMP2/TIMP2比值在Genistein组(0. 498±0.214)显著低于对照组(1 .011±0. 319),P<0 .05。结论 Genistein显著抑制Bel 7402肝癌移植瘤在裸小鼠肾包膜下的侵袭性生长,病理性肿瘤血管生成减少及MMP2表达降低与其抗肿瘤侵袭作用密切相关。

Objective To study the inhibitory effects of genistein on invasive growth of xenograft Bel 7402 hepatocellular carcinoma (HCC) and investigate its underlying mechanism. Methods Ten nude mice were divided into 2 groups. Bilateral subrenal capsule xenograft transplantation of HCC was performed in each nude mouse. Genistein was intraperitoneally injected into the nude mice for 15 days. The invasion of HCC to the renal parenchyma was observed. After the model of transplanted HCC was established, MVD was determined with immunohistochemistry and MMP2 and TIMP2 with RT-PCR. Results Tumor growth in genistein-treated group was significantly retarded as compared with the control group. The increased volume of the tumor, level of MCV expression and level of MMP2 expression were significantly lower in the genistein-treated group than in the control (63.32±8.96 mm 3 vs 79.25±6.85 mm 3, P<0.05;10.422±0.807 vs 22.330±5.696, P<0.05;0.296±0.132 vs 0.519±0.158, P<0.05). There was no significant difference in the level of TIMP2 expression between the 2 groups. However, the MMP2/TIMP2 ratio was markedly lower in the genistein-treated group than in the control (P<0.05). Conclusions Genistein can effectively inhibits the invasive ability of subrenal capsule xenograft Bel 7402 HCC to surrounding tissues in nude mice and decreased pathological angiogenesis and decreased MMP2 expression play an important role in this process.