title: Protective autophagy promotes the resistance of HER2-positive breast cancer cells to lapatinib.
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.
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Suning
authors.initials: S
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an, Shaanxi, 710032, China.|Department of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Xingmei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Qiao
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Ye
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lai
authors.affiliation: Cadet Brigade of the Fourth Military Medical University, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Shentong
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Likun
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. adwen@fmmu.edu.cn.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an, Shaanxi, 710032, China. biozhangj@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D000077341:Lapatinib; D011799:Quinazolines / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Autophagy; Breast cancer; Lapatinib; Resistance