Sensitization of breast cancer cells to paclitaxel by dichloroacetate through inhibiting autophagy

Biochemical and Biophysical Research Communications
Minghao WangJun Jiang

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.

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Citations

Nov 28, 2018·Dose-response : a Publication of International Hormesis Society·Jūratė StanevičiūtėDonatas Stakišaitis
Jun 27, 2019·Cancer Biology & Therapy·Dmitriy OvcharenkoVictor Ovcharenko
Jun 12, 2021·Frontiers in Cell and Developmental Biology·Minjeong YeonDooil Jeoung

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