OncoTargets and Therapy (Aug 2019)

Chelidonine enhances the antitumor effect of lenvatinib on hepatocellular carcinoma cells

  • Hou F,
  • Guo L,
  • Zheng K,
  • Song J,
  • Wang Q,
  • Zheng Y

Journal volume & issue
Vol. Volume 12
pp. 6685 – 6697

Abstract

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Fang-jie Hou, Li-xiao Guo, Kai-yan Zheng, Jun-na Song, Qian Wang, Yu-guang ZhengHebei University of Chinese Medicine, Shijiazhuang City, Hebei Province 050200, People’s Republic of ChinaCorrespondence: Kai-yan ZhengHebei University of Chinese Medicine, No. 3 Xingyuan Road, Luquan Economic Development Zone, Shijiazhuang City, Hebei Province 050200, People’s Republic of ChinaTel +86 311 8992 6017Fax +86 311 8992 6017Email [email protected]: Lenvatinib is a newly approved molecular targeted drug for the treatment of advanced hepatocellular carcinoma (HCC). However, the high cost associated with this treatment poses a huge financial burden on patients and the entire public health system. Therefore, there is an urgent need to develop novel strategies that enhance the antitumor effect of lenvatinib.Methods: The antitumor effects of chelidonine or/and lenvatinib on HCC cell lines MHCC97-H and LM-3 were examined using the 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2- H-tetrazolium bromide (MTT) assay. For the in-vivo investigation, the effect on subcutaneous or intrahepatic tumor growth in nude mice was also determined. The mRNA levels of epithelial mesenchymal transition (EMT)-related factors were examined through quantitative polymerase chain reaction or Western blot.Results: In the present study, we found that treatment with chelidonine enhanced the apoptotic effect of lenvatinib on HCC cells and the in-vivo growth of HCC tumors in nude mice. Mechanistically, treatment with chelidonine increased the expression of epithelial indicator E-cadherin, whereas it decreased the expression of mesenchymal indicators N-cadherin and Vimentin. These findings suggest that chelidonine restricted the EMT in HCC cells.Conclusion: Chelidonine inhibits the process of EMT and enhances the antitumor effect of lenvatinib on HCC cells.Keywords: advanced hepatocellular carcinoma, lenvatinib, chelidonine, epithelial mesenchymal transition

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