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Tumor Biology

, Volume 37, Issue 2, pp 2321–2331 | Cite as

Protective autophagy promotes the resistance of HER2-positive breast cancer cells to lapatinib

  • Suning Chen
  • Xingmei Zhu
  • Hongyu Qiao
  • Mingxiang Ye
  • Xiaofeng Lai
  • Shentong Yu
  • Likun Ding
  • Aidong Wen
  • Jian Zhang
Original Article

Abstract

Lapatinib, a tyrosine kinase inhibitor of HER2/EGFR, can inhibit the proliferation of HER2-positive breast cancer cells. Additionally, the combination of lapatinib and chemotherapy can markedly prolong patient survival time. However, the clinical therapeutic effect of lapatinib is severely limited by drug resistance. We previously found that brief treatment with lapatinib induced both apoptosis and autophagy in HER2-positive breast cancer cells. Additionally, the apoptosis induced by lapatinib was dependent on autophagy. In our current study, however, we used extended treatment of HER2-positive breast cancer cells with lapatinib to confirm the presence of protective autophagy in the previously established lapatinib-resistant cells. Specifically, we found that inhibition of autophagy could reduce the proliferation, DNA synthesis, and colony-forming capacity of resistant cells. Thus, autophagy is a potential novel therapeutic target for reversing lapatinib resistance of HER2-positive breast cancer cells. Our data provide clear, novel evidence of both anti-apoptotic and pro-apoptotic functions of autophagy in breast cancer during lapatinib treatment.

Keywords

Breast cancer Lapatinib Resistance Autophagy 

Abbreviations

BT-474par

Parental BT-474 cells

BT-474LapR

Lapatinib-resistant BT-474 cells

AU-565par

Parental AU-565 cells

AU-565LapR

Lapatinib-resistant AU-565 cells

HER2

Human epidermal growth factor receptor 2

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (81202091, 81402186, and 81102006) and the Natural Science Foundation of Shaanxi Province (2013JC2-21).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Suning Chen
    • 1
  • Xingmei Zhu
    • 2
    • 3
  • Hongyu Qiao
    • 2
  • Mingxiang Ye
    • 2
  • Xiaofeng Lai
    • 2
  • Shentong Yu
    • 4
  • Likun Ding
    • 1
  • Aidong Wen
    • 1
  • Jian Zhang
    • 2
  1. 1.Department of Pharmacy, Xijing HospitalThe Fourth Military Medical UniversityXi’anChina
  2. 2.The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular BiologyThe Fourth Military Medical UniversityXi’anChina
  3. 3.Department of PharmacyShaanxi University of Chinese MedicineXianyangChina
  4. 4.Cadet Brigade of the Fourth Military Medical UniversityThe Fourth Military Medical UniversityXi’anChina

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