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目的:观察非小细胞肺癌(non-small cell lung cancer,NSCLC)患者使用表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)初始治疗失败后,经过一段时间的间歇期,再次应用EGFR-TKI治疗的临床疗效,并探讨其可能的分子机制。方法:回顾性分析2008-12-01-2012-05-30,我院19例初始用EGFR-TKI治疗失败后停止一段时间并再次应用EGFR-TKI治疗的NSCLC患者的临床资料。采用小剂量递增的方法,体外诱导EGFR-TKI耐药的细胞模型,研究“治疗再反应”现象可能的分子机制。结果:19例NSCLC患者中47.4%(9/19)再次应用EGFR-TKI仍可获得疾病控制,其中PR为15.8%(3/19),SD为31.6%(6/19)。同时,体外诱导的耐药细胞株经顺铂治疗2个月后,再次给予厄洛替尼(Erlotinib)治疗,抑制率由3%升高至15%,P<0.05,再次显示了部分的有效性。蛋白质印迹法检测自噬相关分子LC3B发现,耐药细胞株LC3B表达增加,再次Erlotinib治疗后LC3B表达水平相对未处理细胞明显下调。结论:EGFR-TKI治疗失败的NSCLC患者经过一段时间的间歇期再次应用EGFR-TKI,部分患者仍可获得较满意的疾病控制,该效应可能与细胞自噬有密切关系,这种再治疗反应有望成为NSCLC的一种有效治疗策略。
Objective: To observe the failure of initial treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in patients with non-small cell lung cancer (NSCLC) After a period of intermittent, re-application of EGFR-TKI treatment of clinical efficacy, and explore its possible molecular mechanism. Methods: The clinical data of 19 NSCLC patients who had been initially stopped with EGFR-TKI for a period of time and re-applied EGFR-TKI in our hospital from 2008-12-01 to 2012-05-30 were retrospectively analyzed. A small dose escalation method was used to induce a cell model of EGFR-TKI resistance in vitro and to investigate the possible molecular mechanism of the “treatment re-response” phenomenon. Results: Of the 19 NSCLC patients, 47.4% (9/19) were still able to get disease control by re-application of EGFR-TKI. The PR was 15.8% (3/19) and SD was 31.6% (6/19). Meanwhile, the drug-resistant cell lines induced in vitro were treated with cisplatin for 2 months and then treated with erlotinib again. The inhibition rate increased from 3% to 15%, P <0.05, again showing some effective Sex. LC3B detected by Western blotting showed that the expression of LC3B in drug-resistant cell line was increased, and the expression level of LC3B in Erlotinib-treated cells was significantly down-regulated compared with untreated cells. CONCLUSIONS: NSCLC patients with failed EGFR-TKI therapy may re-apply EGFR-TKI intermittently over a period of time, and some patients may still receive more satisfactory disease control, which may be closely related to autophagy. This re-treatment response is expected Become an effective treatment strategy for NSCLC.