bafilomycin-a1 and Tongue-Neoplasms

The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1. Furthermore, we found that cisplatin resistance of TSCC cells was related to cisplatin inducing lysosome biogenesis in a TFEB-dependent manner, which was regulated by c-Abl. In summary, this is the first study to show that Bafilomycin A1 increases the sensitivity of TSCC cells to cisplatin by inhibiting lysosomal function but not autophagy. Lysosomes may be a potential target to increase cisplatin cytotoxicity toward TSCC cells.

Topics: Autophagy; Autophagy-Related Protein 5; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Carcinoma, Squamous Cell; Cell Line, Tumor; Cisplatin; Drug Resistance, Neoplasm; Drug Synergism; Gene Expression Regulation, Neoplastic; Gene Knockout Techniques; Humans; Lysosomes; Macrolides; Platinum; Proto-Oncogene Proteins c-abl; Tongue Neoplasms