• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
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

Effects and mechanisms of AKR1C3 inducing doxorubicin resistance in breast cancer

Funds: This study was supported by the National Natural Science Foundation of China (No.81830105)
More Information
  • Received Date: March 04, 2021
  • Revised Date: May 12, 2021
  • 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.
  • [1]
    . CA Cancer J Clin,2019,69(1):7-34.
    [2]
    Xu ML,Wang C,Wang N,et al. MALAT1 upregulates SMYD3 by competition with miR-124 and promotes proliferation and migration of breast cancer cells[J]. J China Pharm Univ(中国药科大学学报),2019,50(3):344-351.
    [3]
    Greenlee H,Dupont-Reyes MJ,Balneaves LG,et al. Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment[J]. CA Cancer J Clin,2017,67(3):194-232.
    [4]
    Howard GR,Johnson KE,Rodriguez Ayala A,et al. A multi-state model of chemoresistance to characterize phenotypic dynamics in breast cancer[J]. Sci Rep,2018,8(1):12058.
    [5]
    Bandyopadhyay A,Wang L,Agyin J,et al. Doxorubicin in combination with a small TGFbeta inhibitor:a potential novel therapy for metastatic breast cancer in mouse models[J]. PLoS One,2010,5(4):e10365.
    [6]
    Turton NJ,Judah DJ,Riley J,et al. Gene expression and amplification in breast carcinoma cells with intrinsic and acquired doxorubicin resistance[J]. Oncogene,2001,20(11):1300-1306.
    [7]
    Penning TM,Burczynski ME,Jez JM,et al. Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily:functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones[J]. Biochem J,2000,351(Pt 1):67-77.
    [8]
    Penning TM. AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase):roles in malignancy and endocrine disorders[J]. Mol Cell Endocrinol,2019,489:82-91.
    [9]
    Liu Y,He SY,Chen Y,et al. Overview of AKR1C3:inhibitor achievements and disease insights[J]. J Med Chem,2020,63(20):11305-11329.
    [10]
    Boichuk S,Galembikova A,Sitenkov A,et al. Establishment and characterization of a triple negative basal-like breast cancer cell line with multi-drug resistance[J]. Oncol Lett,2017,14(4):5039-5045.
    [11]
    Yamashita N,Kanno Y,Saito N,et al. Aryl hydrocarbon receptor counteracts pharmacological efficacy of doxorubicin via enhanced AKR1C3 expression in triple negative breast cancer cells[J]. Biochem Biophys Res Commun,2019,516(3):693-698.
    [12]
    Ruiz de Galarreta M,Bresnahan E,Molina-Sánchez P,et al. β-catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma[J]. Cancer Discov,2019,9(8):1124-1141.
    [13]
    Tenbaum SP,Ordó?ez-Morán P,Puig I,et al. β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer[J]. Nat Med,2012,18(6):892-901.
    [14]
    Huang SM,Mishina YM,Liu SM,et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling[J]. Nature,2009,461(7264):614-620.
    [15]
    Wu C,Yu S,Tan Q,et al. Role of AhR in regulating cancer stem cell-like characteristics in choriocarcinoma[J]. Cell Cycle,2018,17(18):2309-2320.

Catalog

    Article views (222) PDF downloads (622) Cited by()

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return