FIP-gts potentiate autophagic cell death against cisplatin-resistant urothelial cancer cells

Abstract

Background: Urothelial cancer (UC) is a common cancer among males. Once metastatic or chemoresistant diseases develop, there is little effective treatment available. A fungal immunomodulatory protein, ganoderma tsugae (FIP-gts) possesses antitumor activity against solid tumors and inhibits telomerase activity. FIP-gts induces autophagy in cancer cells and may provide an alternative pathway against chemo-resistance.

Materials and methods: Two UC cell lines were used to investigate the cytotoxicity effects and the autophagy regulation of FIP-gts using flow cytometry, acidic vesicular organelles (AVO) staining and western blotting.

Results: MTT assay showed that FIP-gts and bafilomycin-A1 (Baf-A1) and or chloroquine (CQ) could enhance a significantly synergistic cytotoxicity. The treatment of UC cell lines with FIP-gts activated LC-3 II formation and AVO positive staining on western blot and flow cytometry. Interestingly, FIP-gts and Baf-A1 combined treatment was found to lead to enhancement of apoptosis along with inhibition of autophagy in parental and resistant UC cells.

Conclusion: FIP-gts may have the potential to be utilized as a therapeutic adjuvant for the treatment of resistant UC cancer down-regulating Beclin-1 to activate autophagic cell death.

Keywords: Apoptosis; autophagy; chemo-resistant; urothelial carcinoma.