TMCC3的异常表达通过激活AKT活性介导非小细胞肺癌对吉非替尼耐药  

The abnormal expression of TMCC3 via activation AKT is associated with acquired resistance to gefitinib in non-small cell lung cancer

作　　者：王爽[1] 荣雪竹 王蕊[2] 李珍 黄少冰 刘洋[2] WANG Shuang;RONG Xuezhu;WANG Rui;LI Zhen;HUANG Shaobing;LIU Yang(Department of Anesthesiology,the First Hospital of China Medical University,Liaoning Shenyang 110001,China;Department of Pathology,the First Hospital of China Medical University,Liaoning Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院麻醉科,辽宁沈阳110001 [2]中国医科大学附属第一医院病理科,辽宁沈阳110001

出　　处：《现代肿瘤医学》2022年第24期4415-4420,共6页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:82003119)。

摘　　要：目的:探讨TMCC3的异常表达在介导非小细胞肺癌(non-small cell lung cancer,NSCLC)耐药中的作用。方法:通过免疫组化方法检测NSCLC中TMCC3的表达模式,并分析其与患者吉非替尼疗效的相关性。应用TMCC3-siRNA下调耐药细胞系中TMCC3的表达后,通过Western blot和细胞功能学实验等方法,检测肺癌细胞系的增殖能力。结果:肺癌组织中呈现TMCC3高表达的患者更容易在短期内出现吉非替尼耐药;在肺癌细胞系中,TMCC3的高表达能够显著激活PI3K/AKT信号通路的活性,促进肺癌细胞的增殖能力,减弱肺癌细胞对吉非替尼的敏感性。结论:TMCC3的异常表达在介导NSCLC耐药中发挥着重要作用,有望为寻求预测肺癌TKI疗效的组织学标记物,更好地实现NSCLC的个体化治疗提供科学依据。Objective:To investigate the role of abnormal expression of TMCC3 in mediating non-small cell lung cancer(NSCLC)resistance to gefitinib.Methods:The expression pattern of TMCC3 in NSCLC was detected by immunohistochemistry and its correlation with the efficacy of gefitinib was analysed.Using TMCC3-siRNA to down regulate the expression of TMCC3 in gefitinib-resistant cell lines,we detected the proliferation of lung cancer cell lines by Western blot and cell function experiment.Results:We found that the NSCLC patients with enhanced TMCC3 were found to be more likely to have drug resistance.In lung cancer cell lines,we further confirmed that the high expression of TMCC3 promoted the proliferation of lung cancer cells and weaken the sensitivity to gefitinib by activating the PI3K/AKT signaling pathway.Conclusion:The abnormal expression of TMCC3 plays an important role in mediating the gefitinib resistance of NSCLC.The results provide a scientific basis for seeking histological markers to predict the efficacy of TKI in lung cancer,thus realize the individualized treatment of NSCLC.

关 键 词：TMCC3 非小细胞肺癌 EGFR-TKI耐药 AKT信号通路 

分 类 号：R734.2[医药卫生—肿瘤]