摘要
目的:探讨葫芦素B(cucurbitacin B,CuB)诱导表皮生长因子受体(epidermal growth factor receptor,EGFR)溶酶体降解并通过CIP2A/PP2A/Akt信号轴抑制吉非替尼耐药(gefitinib-resistant,GR)的非小细胞肺癌(nonsmall cell lung cancer,NSCLC)的作用机制。方法:MTT测定CuB和Gefitinib对H1975和H820细胞的抑制作用,Transwell侵袭实验及划痕愈合实验检测细胞转移能力,实时定量PCR检测EGFR基因的表达水平,Western blot检测相关蛋白的表达水平。结果:CuB不仅能抑制GR NSCLC细胞的增殖和侵袭,诱导其凋亡;而且能够促进EGFR溶酶体降解,以及下调CIP2A/PP2A/Akt信号轴。结论:CuB通过诱导EGFR溶酶体降解和下调CIP2A/PP2A/Akt信号轴来抑制GR NSCLC细胞的增殖和侵袭,可能成为治疗GR NSCLC的新型候选药物。
Objective To investigate the role of Cucurbitacin B(CuB) in inducing epidermal growth factor receptor(EGFR) lysosomal degradation and inhibiting gefitinib-resistant non-small cell lung cancer(NSCLC) through CIP2 A/PP2 A/Akt signaling axis. Methods MTT was used to determine the inhibitory effect of CuB and Gefitinib on H1975 and H820 cells. Transwell invasion test and scratch healing test were used to detect cell metastasis ability. Real-time quantitative PCR was used to detect the expression level of EGFR gene. Western blot was used to detect the expression level of the related proteins. Results CuB not only inhibited the proliferation and invasion of GR NSCLC cells, induced apoptosis, but also promoted lysosomal degradation of EGFR and down-regulated the CIP2 A/PP2 A/Akt signal axis. Conclusion CuB can inhibit the proliferation and invasion of GR NSCLC cells by inducing EGFR lysosomal degradation and down-regulating the CIP2 A/PP2 A/Akt signal axis, and may be a new drug candidate for the treatment of GR NSCLC.
作者
杨锐
武明薇
向雨晨
周彤
司渊
刘莹
YANG Rui;WU Ming-wei;XIANG Yu-chen;ZHOU Tong;SI Yuan;LIU Ying(School of Basic Medical Sciences,Hubei University of MedicineShiyan,Hubei 442000,China;Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Hubei University of Medicine,Shiyan,Hubei 442000,China)
出处
《湖北医药学院学报》
CAS
2020年第1期7-15,F0002,共10页
Journal of Hubei University of Medicine
基金
2018年度国家自然科学基金青年项目(81802387)
2019年度湖北省教育厅优秀中青年科技创新团队(T201915)
湖北医药学院研究生科技创新项目(YC2019001)
2019年大学生创新创业训练项目国家级资助(201910929020)。
