敲减骨桥蛋白对吉非替尼耐药的非小细胞肺癌PC9细胞凋亡的研究

doi:10.11904/j.issn.1002-3070.2022.04.004

实用肿瘤学杂志 ›› 2022, Vol. 36 ›› Issue (4): 310-315.doi: 10.11904/j.issn.1002-3070.2022.04.004

敲减骨桥蛋白对吉非替尼耐药的非小细胞肺癌PC9细胞凋亡的研究

温晓星¹, 刘大海², 吴学辉², 王炳平², 房涛²

1.山东省东营市胜利油田中心医院呼吸与危重症医学科(东营 257034);
2.山东省东营市胜利油田中心医院肿瘤科

收稿日期:2021-10-25 修回日期:2022-05-30 出版日期:2022-08-28 发布日期:2022-08-29
通讯作者: 房涛,E-mail:f.t123@163.com
作者简介:温晓星,女,(1989-),硕士,主治医师,从事非小细胞肺癌靶向治疗耐药机制方面的相关研究。
基金资助:
山东省医药卫生科技发展计划项目(编号:2018WS162);山东省自然科学基金(编号:ZR2017PH066)

Knockdown osteopontin promotes gefitinib-resistence PC9 cells apoptosis

WEN Xiaoxing¹, LIU Dahai², WU Xuehui², WANG Bingping², FANG Tao²

1. Department of Pulmonary Medicine,Shengli Oilfield Central Hospital,Dongying 257034,China;
2. Department of Oncology,Shengli Oilfield Central Hospital

Received:2021-10-25 Revised:2022-05-30 Online:2022-08-28 Published:2022-08-29

摘要/Abstract

摘要： 目的研究骨桥蛋白在非小细胞肺癌表皮生长因子酪氨酸激酶抑制剂(EGFR-TKIs)耐药中的作用及作用机制。方法敲减骨桥蛋白的PC9R细胞系为实验组,未作处理的PC9R细胞系为对照组,应用实时定量PCR(qPCR)和免疫蛋白印迹法(Western Blot)检测骨桥蛋白和凋亡相关基因在非小细胞肺癌中的表达。应用线粒体膜电位实验检测非小细胞肺癌细胞的线粒体功能。应用细胞计数试剂盒-8(CCK-8)和细胞增殖检测试剂盒(EdU)实验评估非小细胞肺癌细胞的增殖功能。结果 qPCR及Western Blot实验结果证实与PC9细胞相比,骨桥蛋白在吉非替尼耐药的PC9R细胞中高表达(1.00±0.05 vs. 5.12±0.12,P＜0.01)。敲减骨桥蛋白后引起PC9R细胞的线粒体功能障碍并诱发细胞凋亡(8.34±0.96 vs. 48.56±3.34,P＜0.05),进一步证明敲减骨桥蛋白抑制PC9R细胞的生长、增加肺癌细胞对吉非替尼的敏感性。结论敲减骨桥蛋白诱发线粒体功能障碍促进吉非替尼耐药细胞凋亡。敲减骨桥蛋白增加肺癌细胞对吉非替尼敏感性。

关键词: 骨桥蛋白, 凋亡, 酪氨酸激酶抑制剂, 耐药, 肺癌

Abstract: Objective The aim of this study was to investigate the role and mechanism of osteopontin in mediating epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)resistance in NSCLC.Methods The PC9R cells with osteopontin knockdown was the treatment group,and untreated PC9R cells was the control group.Quantitative real time PCR (RT-qPCR) and Western blot(WB)were carried out to check the expression of osteopontin and apoptosis related proteins in NSCLC cells.Mitochondrial membrane potential measurement assay were performed to check the mitochondria fucntion.The cell counting kit-8(CCK-8)and EdU incorporation assays were used to measure cell proliferation.Results The results showed that osteopontin was significantly up-regulated in gefitinib-resistant PC9R cells compared with PC9 cells(1.00±0.05 vs. 5.12±0.12,P＜0.01).Knockdown of osteopontin induced mitochondria dysfunction and apoptosis related proteins were over expressed(8.34±0.96 vs. 48.56±3.34,P＜0.05).Knockdown of osteopontin inhibted PC9R cells prolifereation.Therefore,our results further demonstrated osteopontin promted PC9R cells apoptosis.Conclusion Knockdown osteopontin induced mitochondrial dysfunction and induced the apoptosis of gefitinib-resistant cells.Knockdown osteopontin increases the sensitivity of lung cancer cells to gefitinib.

Key words: Osteopontin, Apoptosis, Tyrosine kinase inhibitors, Resistance

中图分类号:

R734.1

温晓星, 刘大海, 吴学辉, 王炳平, 房涛. 敲减骨桥蛋白对吉非替尼耐药的非小细胞肺癌PC9细胞凋亡的研究[J]. 实用肿瘤学杂志, 2022, 36(4): 310-315.

WEN Xiaoxing, LIU Dahai, WU Xuehui, WANG Bingping, FANG Tao. Knockdown osteopontin promotes gefitinib-resistence PC9 cells apoptosis[J]. Journal of Practical Oncology, 2022, 36(4): 310-315.

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敲减骨桥蛋白对吉非替尼耐药的非小细胞肺癌PC9细胞凋亡的研究

Knockdown osteopontin promotes gefitinib-resistence PC9 cells apoptosis

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