Protective autophagy promotes the resistance of HER2-positive breast cancer cells to lapatinib
Protective autophagy promotes the resistance of HER2-positive breast cancer cells to lapatinib
复制标题
保护性自噬促进HER2阳性乳腺癌细胞对拉帕替尼的耐药
DOI：
10.1007/s13277-015-3800-9
复制
发表时间：
2016-02-01
期刊：
影响因子：
--
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
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作者：
Chen, Suning;Zhu, Xingmei;Zhang, Jian
拉帕替尼是一种HER 2/EGFR酪氨酸激酶抑制剂，可抑制HER 2阳性乳腺癌细胞的增殖。此外，拉帕替尼联合化疗可显著延长患者生存时间。然而，拉帕替尼的临床治疗效果受到耐药性的严重限制。我们以前发现，拉帕替尼的短暂治疗诱导HER 2阳性乳腺癌细胞的凋亡和自噬。此外，拉帕替尼诱导的细胞凋亡依赖于自噬。然而，在我们目前的研究中，我们使用拉帕替尼延长治疗HER 2阳性乳腺癌细胞，以确认先前建立的拉帕替尼耐药细胞中存在保护性自噬。具体来说，我们发现抑制自噬可以降低耐药细胞的增殖、DNA合成和集落形成能力。因此，自噬是逆转HER 2阳性乳腺癌细胞拉帕替尼耐药性的潜在新治疗靶点。我们的数据为拉帕替尼治疗期间乳腺癌中自噬的抗凋亡和促凋亡功能提供了明确的新证据。
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.