Asian Pacific Journal of Cancer Prevention, 2013, 14(2):759-64.

Genistein Reinforces the Inhibitory Effect of Cisplatin on Liver Cancer Recurrence and Metastasis after Curative Hepatectomy

Peng Chen, Ming-Dao Hu, Xiao-Fan Deng, et al

Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China

BACKGROUND:

The high recurrence rate after hepatic resection in hepatocellular carcinoma (HCC) is a major obstacle to improving prognosis. The objective of the present study was to explore the function of genistein, a soy-derived isoflavone, in enhancing the inhibitory effect of cisplatin on HCC cell proliferation and on tumor recurrence and metastasis in nude mice after curative hepatectomy.

METHODS:

Proliferation of human HCC cells (HCCLM3) was detected by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Synergistic effects of genistein and cisplatin were evaluated with the median-effect formula. Nude mice bearing human HCC xenografts underwent tumour resection (hepatectomy) 10 days post implantation, then received intraperitoneal administration of genistein or cisplatin alone or the combination of the two drugs. 33 days after surgery, recurrent tumours and pulmonary metastasis were evaluated individually. MMP-2 level in recurrent tumours was detected by immunohistochemistry and real-time PCR; MMP-2 expression in HCCLM3 was detected by immunocytochemistry.

RESULTS:

Genistein and cisplatin both suppressed the growth and proliferation of HCCLM3 cells. The two drugs exhibited synergistic effects even at relatively low concentrations. In vivo, mice in the combined genistein and cisplatin group had a smaller volume of liver recurrent tumors and fewer pulmonary metastatic foci compared with single drug treated groups. Cisplatin upregulated the expression of MMP-2 in both recurrent tumours and HCCLM3, while genistein abolished cisplatin-induced MMP-2 expression.

CONCLUSIONS:

Genistein reinforced the inhibitory effect of cisplatin on HCC cell proliferation and tumour recurrence and metastasis after curative hepatectomy in nude mice, possibly through mitigation of cisplatin-induced MMP-2 upregulation.

泰国《亚洲太平洋癌症预防杂志》，2013年

在肝切除术以后金雀异黄素增强了顺铂对肝癌复发和转移的抑制作用

陈鹏，胡明道，邓晓凡，等

中国成都四川大学华西医院肝脏手术科

背景︰

肝切除后的高复发率是改善肝细胞癌 (HCC) 预后的主要障碍。本研究的目的是探讨来源于大豆异黄酮的金雀异黄素，对于增强顺铂对肝切除术后裸鼠的肝癌细胞增殖和肿瘤复发与转移方面的抑制作用的功能。

方法︰

人体肝癌细胞 (HCCLM3)的增殖由MTT 法检测。金雀异黄素与顺铂的协同效应由中位数影响公式计算。在肿瘤切除术 （切除术） 10 天后将人体肝癌移植瘤植入到裸鼠中，然后接受金雀异黄素或顺铂单独或者两种药物结合的腹腔注射。手术33 天以后，分别计算复发性肿瘤和肺转移。复发性肿瘤中的基质金属蛋白酶-2 水平通过免疫组织化学方法和实时荧光 PCR测定；用免疫细胞化学法检测HCCLM3中的基质金属蛋白酶-2的 表达。

结果︰

金雀异黄素与顺铂都能抑制 HCCLM3 细胞的生长与增殖。这两种药物即使在相对较低的浓度下也表现出协同效应。与单药治疗组相比，金雀异黄素和顺铂联合治疗组小鼠，具有体积较小的肝复发肿瘤和较少的肺转移灶。顺铂在复发性肿瘤和 HCCLM3中均上调了基质金属蛋白酶-2的 表达，虽然金雀异黄素抑制了顺铂诱导的基质金属蛋白酶-2 的表达。

结论︰

在裸鼠体内，金雀异黄素，可能通过缓解顺铂诱导的基质金属蛋白酶-2 的上调，在肝切除术后增强顺铂对肝癌细胞增殖和肿瘤复发与转移的抑制作用。