Chinese herbal medicine Feiyanning cooperates with cisplatin to enhance cytotoxicity to non-small-cell lung cancer by inhibiting protective autophagy

Abstract

Ethnopharmacological relevance: Feiyanning (FYN), the Chinese herbal medicine (CHM), has been used to manage non-small cell lung cancer (NSCLC) for the past 23 years. Chemotherapeutic drugs can induce autophagy in cancer cells to protect themselves from death. However, FYN can inhibit the protective autophagy in cancer cells. We investigated the biological mechanisms on the synergistic effects of FYN combined with chemotherapy in lung cancer cells.

Materials and methods: We analyzed the effective chemical components for the quality control of FYN using the UPLC-Q-TOF-MS.The cell proliferation ability was detected by the cell counting kit-8 (CCK-8) and colony formation. The cell apoptosis was determined with Flow cytometry. Expression of important differential proteins were detected by western blot. Autophagy structure was observed by TEM (Tansmission electron microscopy). Tandem mCherry-EGFP-LC3B immunofluorescence was used to measure autophagic flux.

Results: Both FYN and cisplatin significantly induced apoptosis and inhibited cell proliferation in A549 cells. FYN reduced cell viability and increased apoptotic cell populations less effectively than cisplatin. FYN cooperated with cisplatin suppressed the cell viability, colony formation, as well as increased the cell apoptosis rate, and the expression of cleaved caspase-3 and PARP. FYN inhibited autophagy in A549 cells, which characterized by the decrease of autophagosome formation, lysosomal fusion, LC3B-II accumulation and SQSTM1 degradation, down-regulation of ATG5 and ATG7. Protective autophagy in A549 cells was induced by cisplatin. Suppression of the autophagic response using chloroquine (CQ) which is autophagy inhibitor improved the ability of cisplatin to kill cancer cells, as did FYN combined with cisplatin.

Conclusion: In summary, we revealed that the synergistic mechanism of FYN and cisplatin is that FYN inhibited the protective autophagy induced by cisplatin in A549 cells.

Keywords: Autophagy; Chinese herbal medicine; Cisplatin; Feiyanning; Non-small cell lung cancer; Synergistic effect.