Dichloroacetate enhances the antitumor efficacy of chemotherapeutic agents via inhibiting autophagy in non-small-cell lung cancer

Cancer Management and Research
Xiao LuHong Zheng

Abstract

Chemotherapy is still the primary adjuvant strategy of cancer therapy; however, the emergence of multi-drug resistance has been a cause for concern. Autophagy has been demonstrated to have a protective role against chemotherapeutic drugs in cancer cells, and autophagy inhibition is generally considered to be a promising therapeutic strategy. However, the paucity of effective and specific autophagy inhibitors limits its application. The objective of this study was to explore the effect of DCA, small molecular anti-tumor agent, on the autophagy regulation and chemosensitization in NSCLC cells. We investigated the autophagy regulation of dichloroacetate (DCA) by laser confocal microscopy and western blotting in A549 and H1975 cell lines. The MTT assay and flow cytometry was performed for explore the chemosensitization effectiveness of DCA. The results were verified with subcutaneous tumor model in nude mice and the immunohistochemistry was applied for assessing the level of cell apoptosis and autophagy in vivo post treatment. We found that DCA, which exhibited antitumor properties in various carcinoma models, induced apoptosis of non-small cell lung cancer cells (NSCLC) by inhibiting cancer cell autophagy. Furthermore, Perifosine,...Continue Reading

Citations

Dec 13, 2019·Oxidative Medicine and Cellular Longevity·Tiziana Tataranni, Claudia Piccoli
Feb 3, 2021·Advances in Nutrition·Philippe IcardMarco Alifano
Oct 27, 2020·Dose-response : a Publication of International Hormesis Society·Bing HanChengwei He

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Methods Mentioned

BETA
flow cytometry
protein assay
xenograft

Software Mentioned

SPSS

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