Abstract
Abstract Multidrug resistance is the main obstacle in cancer chemotherapy. Emerging evidence has demonstrated the important role of autophagy in cancer cell resistance to chemotherapy. Therefore, autophagy inhibition may be a promising strategy for conquering drug resistance in liver cancer cells. Methods: HepG2/ADM cells were treated with ADCX in the presence or absence of relevant inhibitors, apoptosis was measured by flow-cytometry and expression of autophagy and apoptosis related proteins was detected by western blotting. Confocal microscope was used for GFP-LC3 assay, tandem mRFP-GFP-LC3 assay, DQ-BSA method and colocalization of GFP-LC3 and LAMP1. Celluar ultrastructure was observed by transmission electronic microscopy. Results: ADCX, a natural cycloartane triterpenoid extracted from the traditional Chinese medicine (TCM) source Cimicifugae Rhizoma (Shengma), inhibited autophagic degradation by impairing the maturation of lysosomal cathepsins in multidrug resistant liver cancer HepG2/ADM cells, thereby leading to autophagic flux inhibition. Interestingly, Akt was over-activated by ADCX treatment, which was associated with impairment of cathepsin maturation. Moreover, impairing autophagic degradation promoted ADCX-induced apoptotic cell death in HepG2/ADM cells. Conclusions: Our study indicates that impairing autophagic degradation may be an effective approach for overcoming resistance and also suggests a novel role for Akt in autophagic degradation. Citation Format: NAN YAO, Haiyan Sun, Maohua Huang, Wencai Ye, SiBao Chen, Dong-Mei Zhang. The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4280.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
