Cheong Hio Teng, Xu Fei, Choy Chi Tung, Hui Connie Wun Chun, Mok Tony Shu Kam, Wong Chi Hang
Department of Clinical Oncology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510000, P.R. China.
Oncol Lett. 2018 Jan;15(1):901-907. doi: 10.3892/ol.2017.7377. Epub 2017 Nov 9.
Lung cancer has the highest incidence and mortality rate worldwide among all malignancy-associated mortalities, of which non-small cell lung cancer accounts for 80% of all cases. Resistance against epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) develops following 8-12 months of disease progression, and is a critical issue. HCC827 cell lines with resistance to EGFR-TKIs were successfully screened. The half maximal inhibitory concentration values were 1,000-fold higher than the values for the parental HCC827 cell line, thereby demonstrating cross-resistance against the same family of TKIs. The expression of B-cell lymphoma 2 (Bcl2) was markedly increased in the resistant clones, as well as in the patient biopsies. The phosphatase and tensin homolog phosphoinositide 3-kinase signaling axis is a potential mechanism for acquiring resistance, and therefore targeting Bcl2 may be a useful strategy for further investigations.
在全球所有与恶性肿瘤相关的死亡中，肺癌的发病率和死亡率最高，其中非小细胞肺癌占所有病例的80%。在疾病进展8至12个月后会出现对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的耐药性，这是一个关键问题。成功筛选出对EGFR-TKIs具有耐药性的HCC827细胞系。其半数最大抑制浓度值比亲代HCC827细胞系的值高1000倍，从而证明对同一类TKIs具有交叉耐药性。在耐药克隆以及患者活检样本中，B细胞淋巴瘤2（Bcl2）的表达显著增加。磷酸酶和张力蛋白同源物磷酸肌醇3激酶信号轴是获得耐药性的潜在机制，因此靶向Bcl2可能是进一步研究的有用策略。
