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Bafilomycin A1 increases the sensitivity of tongue squamous cell carcinoma cells to cisplatin by inhibiting the lysosomal uptake of platinum ions but not autophagy.
- Source :
-
Cancer Letters . Jun2018, Vol. 423, p105-112. 8p. - Publication Year :
- 2018
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TONGUE cancer
*SQUAMOUS cell carcinoma
*CANCER cells
*CISPLATIN
*AUTOPHAGY
*PROTEIN metabolism
*CELL lines
*COMPARATIVE studies
*DRUG resistance in cancer cells
*DRUG synergism
*GENES
*GENETIC techniques
*LYSOSOMES
*MACROLIDE antibiotics
*RESEARCH methodology
*MEDICAL cooperation
*PLATINUM
*PROTEINS
*RESEARCH
*EVALUATION research
*PHARMACODYNAMICS
TONGUE tumors
Subjects
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 423
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 128787440
- Full Text :
- https://doi.org/10.1016/j.canlet.2018.03.003