敲降线粒体内膜转运酶8A提升肺癌细胞系PC-9对吉非替尼治疗的敏感性

doi:10.16352/j.issn.1001-6325.2025.08.1073

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (8): 1073-1077.doi: 10.16352/j.issn.1001-6325.2025.08.1073

敲降线粒体内膜转运酶8A提升肺癌细胞系PC-9对吉非替尼治疗的敏感性

陈磊^*, 任伟豪, 王立德

北京大学首钢医院胸外科,北京 100144

收稿日期:2025-04-30 修回日期:2025-06-10 出版日期:2025-08-05 发布日期:2025-07-11
通讯作者: ^*chenlei_sghospital@163.com

Knockdown of translocase of inner mitochondrial membrane 8A enhances gefitinib sensitivity to lung cancer cell line PC-9

CHEN Lei^*,REN Weihao,WANG Lide

Department of Thoracic Surgery, Peking University Shougang Hospital, Beijing 100144, China

Received:2025-04-30 Revised:2025-06-10 Online:2025-08-05 Published:2025-07-11
Contact: ^*chenlei_sghospital@163.com

摘要/Abstract

摘要： 目的探索线粒体内膜转运酶 8A(TIMM8A)在吉非替尼抑制人肺腺癌细胞系PC-9增殖过程中的表达变化及分子机制。方法转染TIMM8A siRNA用于降低TIMM8A在PC-9及吉非替尼耐药PC-9细胞株(PC-9-MTAC)中的表达水平;CCK-8法评估TIMM8A siRNA转染或吉非替尼药物作用后,PC-9及PC-9-MTAC活力变化;QPCR评估TIMM8A在PC-9及PC-9-MTAC中的表达情况。结果吉非替尼能够以浓度依赖的方式抑制PC-9细胞增殖。进一步研究发现:TIMM8A在该过程中表达明显降低,即仅25 nmol/L吉非替尼作用PC-9细胞48 h即可抑制超过50%的TIMM8A表达,而敲低该蛋白表达可显著增强吉非替尼对PC-9细胞增殖的抑制效果(P＜0.05)。与敏感株相比,100 nmol/L吉非替尼作用PC-9-MTAC 48 h仅抑制约30%的TIMM8A表达。并且,抑制TIMM8A表达能够提升PC-9-MTAC细胞对吉非替尼的药物敏感性(P＜0.05)。结论 TIMM8A低表达能够有效提升肺癌细胞PC-9对吉非替尼的敏感性。

关键词: 肺癌, 靶向治疗, 吉非替尼, 耐药, TIMM8A

Abstract: Objective To explore the alteration and function of TIMM8A during gefitinib-induced growth inhibition of lung cancer cell line PC-9. Methods TIMM8A siRNA transfection experiment was used to inhibit the expression of TIMM8A in PC-9 and gefitinib resistant PC-9 cells (PC-9-MTAC). CCK-8 assay was carried out to assess PC-9 and PC-9-MTAC cell viability after gefitinib treatment or TIMM8A siRNA transfection. qPCR was used to determine TIMM8A expression in PC-9 or PC-9-MTAC cells. Results Gefitinib inhibited PC-9 cell growth in a dose-dependent manner. The expression of TIMM8A was inhibited during this process, and more than 50% TIMM8A expression had been inhibited by 25 nmol/L gefitinib, while knockdown of TIMM8A enhanced inhibitory effects of gefitinib on PC-9 cell proliferation(P＜0.05). Compared with the sensitive cells, treatment of the gefitinib-resistant PC-9-MTAC with 100 nmol/L gefitinib for 48 h only inhibited approximately 30% of TIMM8A expression. Furthermore, inhibition of TIMM8A expression enhanced the sensitivity of PC-9-MTAC cells to gefitinib(P＜0.05). Conclusions Low expression of TIMM8A improves anti-tumor effects of gefitinib in lung cancer cell line PC-9.

Key words: lung cancer, targeted therapy, gefitinib, drug resistance, TIMM8A

中图分类号:

陈磊, 任伟豪, 王立德. 敲降线粒体内膜转运酶8A提升肺癌细胞系PC-9对吉非替尼治疗的敏感性[J]. 基础医学与临床, 2025, 45(8): 1073-1077.

CHEN Lei,REN Weihao,WANG Lide. Knockdown of translocase of inner mitochondrial membrane 8A enhances gefitinib sensitivity to lung cancer cell line PC-9[J]. Basic & Clinical Medicine, 2025, 45(8): 1073-1077.

参考文献

[1] Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024, 4:47-53.
[2] Wu Z, Jiao M, Shu C, et al. Integrin αVβ1-activated PYK2 promotes the progression of non-small-cell lung cancer via the STAT3-VGF axis[J]. Cell Commun Signal, 2024, 22:313. doi: 10.1186/s12964-024-01639-1.
[3] Wu J, Lin Z. Non-small cell lung cancer targeted therapy: drugs and mechanisms of drug resistance[J]. Int J Mol Sci, 2022, 23:15056. doi: 10.3390/ijms232315056.
[4] Nurwidya F, Takahashi F, Takahashi K. Gefitinib in the treatment of nonsmall cell lung cancer with activating epidermal growth factor receptor mutation[J]. J Nat Sci Biol Med, 2016,7:119-123.
[5] Chen M, Li B, Zhang E, et al. Potential roles of tumor microenvironment in gefitinib-resistant non-small cell lung cancer: A narrative review[J]. Medicine (Baltimore), 2023, 102:e35086. doi: 10.1097/MD.0000000000035086.
[6] Hsieh P, Wu Y, Huang C, et al. Comparison of T790M acquisition after treatment with first- and second-genera-tion tyrosine-kinase inhibitors: A systematic review and network meta-analysis[J]. Front Oncol, 2022, 12:869390. doi: 10.3389/fonc.2022.869390.
[7] Arnoult D, Rismanchi N, Grodet A, et al. Bax/Bak-dependent release of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death[J]. Curr Biol, 2005,15:2112-2118.
[8] Roesch K, Curran S, Tranebjaerg L, et al. Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex[J]. Hum Mol Genet, 2002, 11:477-486.
[9] Chi Y, Hirachan S, Zhou Y, et al. Exploring the oncogenic potential of TIMM8A: a crucial factor in breast cancer tumorigenesis[J]. Clin Breast Cancer, 2024, 24:e333-e349.e1. doi: 10.1016/j.clbc.2024.02.011.
[10] Nishimura T, Nakata A, Chen X, et al. Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2[J]. Oncogene, 2019, 38:2464-2481.
[11] Yao X, Roberts N, Iheukwumere P, et al. TLE1 corepressor promotes gefitinib resistance in lung cancer A549 cells via E-cadherin silencing[J]. Biomed Rep, 2024, 22:36. doi: 10.3892/br.2024.1914.
[12] Lin X, Ye R, Li Z, et al. KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/ MAPK pathway in an m6A-dependent manner[J]. Drug Resist Updat, 2023, 66:100908. doi: 10.1016/j.drup.2022.100908.
[13] Zhu X, Yuan Z, Cheng S, et al. TIMM8A is associated with dysfunction of immune cell in BRCA and UCEC for predicting anti-PD-L1 therapy efficacy[J]. World J Surg Oncol, 2022, 20:336. doi: 10.1186/s12957-022-02736-6.
[14] Zhang Y, Lin L, Wu Y, et al. Upregulation of TIMM8A is correlated with prognosis and immune regulation in BC[J]. Front Oncol, 2022, 12:922178. doi: 10.3389/fonc.2022.922178.

[1]	黄倩倩, 贾玉芳, 余华军, 陈融融, 陈丽丽, 伍俊, 张海涛. 用 CRISPR/Cas 9技术构建ACSS3基因稳定敲除的肺癌细胞株[J]. 基础医学与临床, 2025, 45(8): 1016-1021.
[2]	杨瑞, 杜斯奋, 蒋乐辉, 付恬, 任鹏举, 蒋澄宇, 张艳丽. 基于网络药理学的抗肺癌茶叶小分子筛选及验证[J]. 基础医学与临床, 2025, 45(7): 939-946.
[3]	楼海均, 童卓云, 张振宇, 阿合叶尔克·马合沙提, 孟·孟根, 乌都木丽. 敲低DRAM2抑制肺癌细胞系A549的增殖和迁移[J]. 基础医学与临床, 2025, 45(2): 197-202.
[4]	高艺丹, 蒋雪涵, 张红, 杨沛然. 靶向异常通路的动脉性肺动脉高压新型药物研发[J]. 基础医学与临床, 2024, 44(8): 1088-1093.
[5]	郑红, 陈晓霞, 韩李周, 陈苗, 皇甫娟. 降低lncRNA-RMRP表达抑制人肺癌细胞系A549的增殖和侵袭[J]. 基础医学与临床, 2024, 44(7): 974-978.
[6]	宋丽丽, 管玉洁, 马平, 李宁. 急性髓系白血病患儿柔红霉素耐药与PD-L1蛋白表达相关[J]. 基础医学与临床, 2024, 44(6): 833-839.
[7]	段然, 李青原, 冯同. 代谢重编程在特发性肺纤维化发病中的作用[J]. 基础医学与临床, 2024, 44(6): 882-886.
[8]	操辰新, 唐辉, 耿瑞璇, 郭伏平, 白春梅, 王颖轶, 李太生. 循环CD4⁺CD45RA⁺CD62L⁺ T细胞与接受EGFR-TKI治疗的转移性非小细胞肺癌预后相关[J]. 基础医学与临床, 2024, 44(5): 658-664.
[9]	梁香存, 魏小雨, 梁健, 王庆, 耿广. 安罗替尼通过调控miR-16-5p/PD-1轴抑制人非小细胞肺癌细胞系增殖并促进凋亡[J]. 基础医学与临床, 2024, 44(4): 503-512.
[10]	杨铠菲, 朱静格, 张洋洋, 赵俊果, 高雨悦, 胡焕焕, 姬国杰. 索拉菲尼诱导的细胞凋亡和自噬对HeLa细胞耐药性的影响[J]. 基础医学与临床, 2024, 44(4): 467-473.
[11]	王子豪, 夏小超, 李舜. 跨膜蛋白质在恶性肿瘤中作用的研究进展[J]. 基础医学与临床, 2024, 44(3): 398-402.
[12]	张婧, 杨自更, 蔡文琴, 曹维维, 韦红梅, 薛茜茜, 吴宾. 抑制抗增殖蛋白2增强非小细胞肺癌细胞系A549对厄洛替尼敏感性[J]. 基础医学与临床, 2024, 44(3): 325-332.
[13]	李娟, 李晓峰, 徐生志, 唐凯. 华蟾素胶囊联合多西紫杉醇+顺铂化疗用于非小细胞肺癌患者的疗效[J]. 基础医学与临床, 2024, 44(2): 247-251.
[14]	丁飞, 王洒, 黄常新. 非小细胞肺癌患者血清CA211水平和NK细胞数与预后相关[J]. 基础医学与临床, 2024, 44(2): 180-184.
[15]	张进芳, 钟明艳, 杨泉, 冯贝, 李兴东. 下调ATM/hnRNPK信号降低髓系白血病细胞阿霉素耐药[J]. 基础医学与临床, 2024, 44(12): 1638-1643.

敲降线粒体内膜转运酶8A提升肺癌细胞系PC-9对吉非替尼治疗的敏感性

Knockdown of translocase of inner mitochondrial membrane 8A enhances gefitinib sensitivity to lung cancer cell line PC-9

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价