title: Na+/K+-ATPase α3 mediates sensitivity of hepatocellular carcinoma cells to bufalin.
abstract: Bufalin, a major bioactive component of the Chinese medicine Chansu, has been reported to exhibit significant antitumor activity against various cancer cell lines. However, the exact mechanism remains unclear. In this study, we demonstrated that bufalin inhibited the growth of hepatocellular carcinoma (HCC) cells in a dose-dependent manner, which correlated with the expression level of Na+/K+-ATPase α3 in HCC cells. The IC50 of bufalin markedly increased when Na+/K+-ATPase α3 was silenced by RNA interference. Furthermore, we show that bufalin increased the phosphorylation of Akt and ERK1/2 while inhibited FoxO3a expression. Thus, our study suggests that Na+/K+-ATPase α3 might serve as a therapeutic target for bufalin in HCC, and its expression status may help predict sensitivity of HCC cells to bufalin treatment.
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
authors.forename: Huaxing
authors.initials: H
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.forename: Luming
authors.initials: L
authors.lastname: Liu
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cohen
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Meng
authors.forename: Peiying
authors.initials: P
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002018:Bufanolides / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: C488756:ATP1A3 protein, human; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002018:Bufanolides; D034741:RNA, Small Interfering; D000254:Sodium-Potassium-Exchanging ATPase; C022777:bufalin