Advanced Search
HU Xiaohong, BAI Hua, DUAN Juanjuan, LEI Xiu, ZHANG Qifang. Feedback Activation of STAT3 Confers Resistance of HER2-positive Breast Cancer Cells to Lapatinib[J]. Cancer Research on Prevention and Treatment, 2019, 46(4): 305-310. DOI: 10.3971/j.issn.1000-8578.2019.18.1410
Citation: HU Xiaohong, BAI Hua, DUAN Juanjuan, LEI Xiu, ZHANG Qifang. Feedback Activation of STAT3 Confers Resistance of HER2-positive Breast Cancer Cells to Lapatinib[J]. Cancer Research on Prevention and Treatment, 2019, 46(4): 305-310. DOI: 10.3971/j.issn.1000-8578.2019.18.1410

Feedback Activation of STAT3 Confers Resistance of HER2-positive Breast Cancer Cells to Lapatinib

  • Objective To explore the role of interleukin-6 (IL-6) in lapatinib-resistant HER2-positive breast cancer cells BT-474.
    Methods Lapatinib-resistant BT-474 (BT-474R) cells were established. Western blot was used to test P-gp expression. The growth inhibition rate(IC50) was tested by MTT assay, and Caspase 3/7 enzymatic activity levels in parental BT474 and BT-474R cells were investigated by Caspase-Glo® 3/7 assay kit. The apoptotic rate of BT-474R cells infected by siRNA STAT3 was tested by flow cytometry. The protein expression levels of IL-6, P-STAT3, STAT3 and Cleaved Caspase 3 were assayed by Western blot. Caspase 3/7 Glo assay and Annexin V-FITC/PI were used to assay cellular apoptosis.
    Results BT-474R cells displayed significantly elevated P-gp expression when compared with BT-474 cells. Lapatinib treatment stimulated signal transducer and activator of transcription 3 (STAT3) activity, and STAT3 activity was also upregulated in BT-474R cells. STAT3 silencing not only remarkably restored sensitivity to lapatinib and enhanced lapatinib-induced cleaved caspase 3 and cspase3/7 enzymatic activity, but also increased the apoptosis of BT-474R cells (P < 0.01). Furthermore, lapatinib-mediated IL-6 secretion regulated STAT3 activity. Blocking IL-6 using anti-IL-6 antibody abrogated lapatinib-induced STAT3 activity.
    Conclusion Lapatinib-induced IL-6 secretion enhances the resistance through STAT3 signaling in HER2-positive breast cancer cells.
  • loading

Catalog

    Turn off MathJax
    Article Contents

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return