Osthole resensitizes CD133+ hepatocellular carcinoma cells to cisplatin treatment via PTEN/AKT pathway

Abstract

The population of CD133 positive cancer cells has been reported to be responsible for drug resistance of hepatocellular carcinoma (HCC). However, the potential molecular mechanism by which CD133+ HCC cells develop drug resistance is still unclear. In this study, we found that CD133+ HepG2 and Huh7 cells were resistant to cisplatin treatment, compared to the CD133- HepG2 and Huh7 cells. However, treatment with osthole, a natural coumarin isolated from umbelliferae plant monomers, was found to resensitize CD133+ HepG2 and Huh7 cells to cisplatin treatment. In the mechanism research, we found that treatment with osthole increased the expression of PTEN. As a result, osthole inhibited the phosphorylation of AKT and Bad to decrease the amount of free Bcl-2 in CD133+ HepG2 and Huh7 cells. Finally, cisplatin-induced mitochondrial apoptosis was expanded. In conclusion, combination treatment with osthole can resensitize CD133+ HCC cells to cisplatin treatment via the PTEN/AKT pathway.