1. Sensitization of breast cancer cells to paclitaxel by dichloroacetate through inhibiting autophagy.
- Author
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Wang M, Liao C, Hu Y, Qinwen Pan, and Jiang J
- Subjects
- Cell Proliferation drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Doxorubicin antagonists & inhibitors, Doxorubicin pharmacology, Drug Screening Assays, Antitumor, Female, Humans, Structure-Activity Relationship, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Autophagy drug effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Dichloroacetic Acid pharmacology, Paclitaxel pharmacology
- Abstract
Chemotherapy is still the main adjuvant strategy in the treatment of cancer, however, chemoresistance is also frequently encountered. Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that dichloroacetate (DCA), a small molecule compound, could significantly inhibit the autophagy induced by Doxorubicin in breast cancer cells. And DCA markedly enhances Doxorubicin-induced breast cancer cell death and anti-proliferation in vitro. But the sensitization to Dox of DCA was significantly reduced through induction of autophagy by rapamycin. Moreover, the combined therapy of Dox and DCA could significantly inhibit tumor growth in vivo and prolong mouse survival time. Taken together, we demonstrate that DCA could inhibit doxorubicin-inducing autophagy and provide a novel strategy for improving the anti-cancer efficacy of chemotherapy., (Copyright © 2017. Published by Elsevier Inc.)
- Published
- 2017
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