Inhibition of autophagy by 3-MA potentiates cisplatin-induced apoptosis in esophageal squamous cell carcinoma cells
- 30 December 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Medical Oncology
- Vol. 28 (1), 105-111
- https://doi.org/10.1007/s12032-009-9397-3
Abstract
Cisplatin (DDP)-based adjuvant chemotherapy is widely used for the treatment of esophageal cancer. However, DDP resistance has become more common and thus new approaches are required to be explored. Cisplatin was used to induce autophagy in the human esophageal cancer cell line, EC9706 cells, and the effect of autophagy on the survival of EC9706 cells was investigated using an autophagy inhibitor 3-MA. Cell viability was measured by CCK8 assay. Apoptosis and cell cycle were detected by flow cytometry. Monodansylcadaverine (MDC) was used to detect autophagy. Western blotting assay was used to investigate the molecular changes that occurred in the course of treatment. DDP inhibited cell proliferation, induced cell death and cell cycle arrest at S phage. Moreover, autophagy was activated through class III PI3K pathway. The expression of autophagy-related Beclin1 and LC3-I was up-regulated and part of LC3-I was converted into LC3-II. However, after the combination treatment of 3-MA and DDP, the cell inhibitory rate increased; the apoptosis rate and the numbers of cells in S phase also increased. Furthermore, the accumulation of autophagic vacuoles was decreased; the expression of Beclin1 and LC3 was significantly down-regulated and the release of cytochrome c was decreased. DDP-induced apoptosis in EC9706 cells can be enhanced by the inhibitor of autophagy, 3-MA. Autophagy might play a role as a self-protective mechanism in DDP-treated esophageal cancer cells, and its inhibition could be a novel strategy for the adjuvant chemotherapy of esophageal cancer.Keywords
This publication has 37 references indexed in Scilit:
- Role and regulation of autophagy in cancerBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2009
- Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotesCell Death & Differentiation, 2009
- Beclin-1 Expression is a Predictor of Clinical Outcome in Patients with Esophageal Squamous Cell Carcinoma and Correlated to Hypoxia-Inducible Factor (HIF)-1α ExpressionPathology and Oncology Research, 2009
- Autophagy in the Pathogenesis of DiseaseCell, 2008
- Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesisGenes & Development, 2007
- Molecular mechanisms of resistance and toxicity associated with platinating agentsCancer Treatment Reviews, 2007
- Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesisCancer Cell, 2006
- Sulforaphane Causes Autophagy to Inhibit Release of Cytochrome c and Apoptosis in Human Prostate Cancer CellsCancer Research, 2006
- Cisplatin: mode of cytotoxic action and molecular basis of resistanceOncogene, 2003
- LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processingThe EMBO Journal, 2000