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WANG Kaizhen, YANG Wanwan, XU Shengyao, GUO Qinglong, ZHAO Li. Effects and mechanisms of AKR1C3 inducing doxorubicin resistance in breast cancer[J]. Journal of China Pharmaceutical University, 2021, 52(3): 352-360. DOI: 10.11665/j.issn.1000-5048.20210313
Citation: WANG Kaizhen, YANG Wanwan, XU Shengyao, GUO Qinglong, ZHAO Li. Effects and mechanisms of AKR1C3 inducing doxorubicin resistance in breast cancer[J]. Journal of China Pharmaceutical University, 2021, 52(3): 352-360. DOI: 10.11665/j.issn.1000-5048.20210313
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Effects and mechanisms of AKR1C3 inducing doxorubicin resistance in breast cancer

  • School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81830105)
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  • Received Date: March 04, 2021
  • Revised Date: May 12, 2021
    Graphical Abstract
    • Abstract
  • To explore the mechanisms by which AKR1C3 induces tumor resistance, human breast cancer cell strain MCF-7/DOX resistant to doxorubicin, MCF-7/ AKR1C3 cells for overexpression of AKR1C3 and MCF-7/DOX-KD cells for knockdown of AKR1C3 in MCF-7/DOX cells were established. Western blot analysis found that AKR1C3 was expressed at a higher level in MCF-7/DOX than MCF-7 wild type cells. Similarly, CCK-8 and DAPI confirmed that MCF-7/ AKR1C3 cells were more resistant to DOX than AKR1C3 wild types as the IC50 was increased 6 times in MCF-7/AKR1C3 cells more than in AKR1C3 wild type cells. Meanwhile, colony formation ability was also enhanced after AKR1C3 was over-expressed in MCF-7 cells.Cytoplasmic/nuclear separation analysis and IF further found that β-catenin nuclear translocation mediated by AKR1C3 was the main reason contributing to the occurrence of DOX-resistant breast cancer cells. β-catenin inhibitor, XAV939, could reverse the AKR1C3 induced doxorubicin resistance in MCF-7 cells.Results indicated that AKR1C3 could be a potential therapeutic target in breast cancer cells.
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    • References (15)
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