Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Genistein Reinforces the Inhibitory Effect of Cisplatin on Liver Cancer Recurrence and Metastasis after Curative Hepatectomy

  • Chen, Peng (Department of Liver Surgery, West China Hospital of Sichuan University) ;
  • Hu, Ming-Dao (Department of Hepato-biliary Surgery, the 2nd Affiliated Hospital of Kunming Medical College) ;
  • Deng, Xiao-Fan (Department of Liver Surgery, West China Hospital of Sichuan University) ;
  • Li, Bo (Department of Liver Surgery, West China Hospital of Sichuan University)
  • Published : 2013.02.28
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Abstract

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.

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References

  1. Alisi A, Balsano C (2007). Enhancing the efficacy of hepatocellular carcinoma chemotherapeutics with natural anticancer agents. Nutr Rev, 65, 550-3. https://doi.org/10.1111/j.1753-4887.2007.tb00280.x
  2. Banerjee S, Li Y, Wang Z, et al (2008). Multi-targeted therapy of cancer by genistein. Cancer Lett, 269, 226-42. https://doi.org/10.1016/j.canlet.2008.03.052
  3. Bosch FX, Ribes J, Diaz M, et al (2004). Primary liver cancer: worldwide incidence and trends. Gastroenterology, 127, S5-16. https://doi.org/10.1053/j.gastro.2004.09.011
  4. Chou TC, Talalay P (1984). Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul, 22, 27-55. https://doi.org/10.1016/0065-2571(84)90007-4
  5. Cohen JH, Kristal AR, Stanford JL (2000). Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst, 5, 61-8.
  6. D'Anna R, Cannata ML, Atteritano M, et al (2007). Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study. Menopause, 14, 648-55. https://doi.org/10.1097/01.gme.0000248708.60698.98
  7. De Larco JE, Wueatz BR, Manivel JC, et al (2001). Progression and enhancement of metastatic potential after exposure of tumor cells to chemotherapeutic agents. Cancer Res, 1, 2857-61.
  8. Giannelli G, Bergamini C, Marinosci F, et al (2002). Clinical role of MMP-2/TIMP-2 imbalance in hepatocellular carcinoma. Int J Cancer, 97, 425-31. https://doi.org/10.1002/ijc.1635
  9. Gurib-Fakim A (2006). Medicinal plants: traditions of yesterday and drugs of tomorrow. Mol Asp Med, 1, 1-93.
  10. Gu Y, Zhu CF, Dai YL, et al (2009). Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma. World J Gastroentero, 15, 4952-7. https://doi.org/10.3748/wjg.15.4952
  11. Kumi-Diaka J, Merchant K, Haces A (2010). Genistein-selenium combination induces growth arrest in prostate cancer cells. J Med Food, 13, 842-50. https://doi.org/10.1089/jmf.2009.0199
  12. Jian Z, Tang ZY, Jia F, et al (2003). Capecitabine inhibits postoperative recurrence and metastasis after liver cancer resection in nude mice with relation to the expression of platelet-derived endothelial cell growth factor. Clin Cancer Res, 18, 6030-7.
  13. Lakshman M, Xu L, Ananthanarayanan V, et al (2008). Dietary genistein inhibits metastasis of human prostate cancer in mice. Cancer Res, 68, 2024-32. https://doi.org/10.1158/0008-5472.CAN-07-1246
  14. Lamartiniere CA (2002). Timing of exposure and mammary cancer risk. J Mammary Gland Biol Neoplasia, 7, 67-76. https://doi.org/10.1023/A:1015722507237
  15. Latifi A, Abubaker K, Castrechini N (2011). Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile. Cell Biochem, 112, 2850-64 https://doi.org/10.1002/jcb.23199
  16. Li Y, Ahmed F, Ali S, et al (2005). Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res, 65, 6934-42. https://doi.org/10.1158/0008-5472.CAN-04-4604
  17. Li Y, Tang Y, Ye L, et al (2003). Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol, 129, 43 -51.
  18. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  19. Llovet JM, Burroughs A, Bruix J (2003). Hepatocellular carcinoma. Lancet, 362, 1907-17. https://doi.org/10.1016/S0140-6736(03)14964-1
  20. Parkin DM, Pisani P, Ferlay J (1999). Global cancer statistics. CA Cancer J Clin, 49, 33-64. https://doi.org/10.3322/canjclin.49.1.33
  21. Sarkar FH, Li Y (2003). Soy isoflavones and cancer prevention. Cancer Invest, 21, 744-57. https://doi.org/10.1081/CNV-120023773
  22. Sun FX, Tang ZY, Lui KD, et al (1996). Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer, 66, 239-43. https://doi.org/10.1002/(SICI)1097-0215(19960410)66:2<239::AID-IJC17>3.0.CO;2-7
  23. Sherman M (2005). Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis, 25, 143-54. https://doi.org/10.1055/s-2005-871194
  24. Tang ZY (2000). Surgery of hepatocellular carcinoma with special reference to studies on metastasis and recurrence. Gastroenterol Today, 4, 191-5.
  25. Tang ZY, Yu YQ, Zhou XD, et al (1998). Progress and prospects in hepatocellular carcinoma surgery. Ann Chir, 52, 558-63.
  26. Vihinen P, Ala-aho R, Kahari VM (2005). Matrix metalloproteinases as therapeutic targets in cancer. Curr Cancer Drug Targets, 5, 203-20. https://doi.org/10.2174/1568009053765799
  27. Wang L, Wu WZ, Sun HC, et al (2003). Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J Gastrointest Surg, 7, 587-94. https://doi.org/10.1016/S1091-255X(03)00072-6
  28. Xiao CL, Tao ZH, Guo L, et al (2011). Isomalto oligosaccharide sulfate inhibits tumor growth and metastasis of hepatocellular carcinoma in nude mice. BMC Cancer, 11, 150-61 https://doi.org/10.1186/1471-2407-11-150
  29. Yamamoto J, Kosuge T, Takayama T, et al (1996). Recurrence of hepatocellular carcinoma after surgery. Br J Surg, 83, 1219-22. https://doi.org/10.1002/bjs.1800830913
  30. Yang JM, Xu Z, Wu H, et al (2003). Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells. Mol Cancer Res, 1, 420-7.
  31. Yang R, Rescorla FJ, Reilly CR, et al (1992). A reproducible rat liver cancer model for experimental therapy: introducing a technique of intrahepatic tumor implantation. J Surg Res, 52, 193-8. https://doi.org/10.1016/0022-4804(92)90072-8
  32. Ye JZ, Miao ZG, Wu FX, et al (2012). Recurrence after anatomic resection versus nonanatomic resection for hepatocellular carcinoma: a meta-analysis. Asian Pac J Cancer Prev, 13, 1771-7. https://doi.org/10.7314/APJCP.2012.13.5.1771
  33. Yeh TC, Chiang PC, Li TK, et al (2007). Genistein induces apoptosis in human hepatocellular carcinomas via interaction of endoplasmic reticulum stress and mitochondrial insult. Biochem Pharmacol, 73, 782-92. https://doi.org/10.1016/j.bcp.2006.11.027
  34. Yin M, Dhir R, Parwani AV, et al (2007). Diagnostic utility of p501s (prostein) in comparison to prostate specific antigen (PSA) for the detection of metastatic prostatic adenocarcinoma. Diagn Pathol, 2, 41-6. https://doi.org/10.1186/1746-1596-2-41

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