Co-delivery of sorafenib and metapristone encapsulated by CXCR4-targeted PLGA-PEG nanoparticles overcomes hepatocellular carcinoma resistance to sorafenib.

ABSTRACT:

Background

Sorafenib is approved as a standard therapy for advanced hepatocellular carcinoma (HCC), but its clinical application is limited due to moderate therapeutic efficacy and high incidence of acquired resistance resulted from elevated levels of SDF-1/CXCR4 axis induced by prolonged sorafenib treatment. We previously demonstrated metapristone (RU486 metabolite) as a cancer metastatic chemopreventive agent targeting SDF-1/CXCR4 axis. Therefore, we hypothesized that combining sorafenib with metapristone could synergistically suppress cell proliferation, enhance anti-cancer activity and repress potential drug resistance.

Methods

Changes in cellular CXCR4 expression by metapristone were analyzed by RT-PCR and western blotting. Effect of combining sorafenib with metapriston

SUBMITTER: Zheng N 

PROVIDER: S-EPMC6544999 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature