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Research Paper|Volume 12, Issue 14|pp 14406—14417

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

Junfeng Ye1, Di Sun2, Ying Yu1, Jinhai Yu3
  • 1Department of Hepato-Biliary-Pancreatic Surgery, First Hospital Jilin University, Changchun 130021, Jilin Province, China
  • 2Department of Colorectal and Anal Surgery, First Hospital Jilin University, Changchun 130021, Jilin Province,130021, China
  • 3Department of Gastrointestinal Surgery, First Hospital Jilin University, Changchun 130021, Jilin Province, China
Received: February 28, 2020Accepted: May 27, 2020Published: July 16, 2020
https://doi.org/10.18632/aging.103484

Copyright: © 2020 Ye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.