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. 2021 Jul 15;11:697950. doi: 10.3389/fonc.2021.697950

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Copyright © 2021 Li, Chen, Chen, Hu, Yang, Zhuo, Chen, Yang, Zhou, Mao, Zhang, Xu, Ju, Shen, Wang, Dong, Xie, Wei, Jia, Zhou and Wang

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Pimozide sensitizes DOX-resistant cells to DOX by suppressing STAT5a. (A) Survival rate of MCF/DOX cells after treatment with pimozide for 48 h, with the IC50 calculated to be 14.79 μM. (B, C) Expression of p-STAT5 (Try 694), STAT5a and ABCB1 in MCF7/DOX cells after treatment with 0, 1, 2, or 5 μM DOX for 48 h (B) or with 5 μM DOX for 0, 12, 24, 48 or 72 h (C). (D) Survival rate of MCF/DOX cells after treatment with a combination of 0, 1, 2 or 5 μM pimozide and the indicated concentration of DOX for 48 h. (E, F) Apoptosis rate of MCF7/DOX cells after the indicated treatment assessed by flow cytometry (E); bar graphs showing the percentage of apoptotic cells (F). (G) Expression of apoptosis markers in MCF7/DOX cells given the indicated treatments determined by Western blotting. (H, I) Accumulation of DOX in MCF7/DOX cells after treatment with DOX or a combination of DOX and pimozide (H) and quantification (I). (J, K) Western blotting was performed to determine the expression of STAT5a, ABCB1, cleaved PARP, cleaved caspase 7 and cleaved caspase 3 in MCF7/DOX cells treated with DOX and transfected with the indicated vectors. ns, p > 0.05; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.