雷公藤甲素对非小细胞肺癌细胞系A549增殖的抑制和凋亡的诱导

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (3): 315-320.

雷公藤甲素对非小细胞肺癌细胞系A549增殖的抑制和凋亡的诱导

刘倩^1*, 汤建华¹, 张志华²

1.河北北方学院附属第一医院药学部, 河北张家口 075000;
2.河北北方学院附属第一医院呼吸内科, 河北张家口 075000

收稿日期:2019-03-26 修回日期:2019-09-30 出版日期:2020-03-05 发布日期:2020-03-02
通讯作者: ^*nings570@163.com
基金资助:
2018年度河北省医学科学研究重点课题计划(20180828)

Triptolide inhibits the proliferation and promotes apoptosis of non-small cell lung cancer cell line A549

LIU Qian^1*, TANG Jian-hua¹, ZHANG Zhi-hua²

1. Pharmacy Department;
2. Department of Respiratory Medicine, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China

Received:2019-03-26 Revised:2019-09-30 Online:2020-03-05 Published:2020-03-02
Contact: ^*nings570@163.com

摘要/Abstract

摘要： 目的探讨雷公藤甲素(TP)通过调控趋化因子受体4(CXCR4)基因表达对人非小细胞肺癌(A549)细胞增殖和凋亡的影响。方法实验分为4组:对照组、TP组(100 nm/L TP处理细胞)、CXCR4+TP组(转染质粒及TP处理细胞)和NC+TP组(转染空载质粒及TP处理细胞)。RT-qPCR和Western blot检测CXCR4表达以及转染效果;MTT法检测细胞增殖;Annexin Ⅴ-FITC/PI双染色法检测细胞凋亡;Western blot检测增殖及凋亡相关蛋白表达。结果雷公藤甲素能够抑制A549细胞中CXCR4 mRNA和蛋白的表达(P＜0.05)。雷公藤甲素可抑制A549细胞增殖,诱导其凋亡(P＜0.05)。转染pcDNA-CXCR4能够上调CXCR4 mRNA和蛋白的表达(P＜0.05)。上调CXCR4的表达能够部分逆转雷公藤甲素对A549细胞增殖抑制和凋亡诱导的作用(P＜0.05)。结论雷公藤甲素可能通过下调CXCR4的表达抑制A549细胞增殖,诱导细胞凋亡。

关键词: 雷公藤甲素, CXCR4基因, 非小细胞肺癌细胞系A549, 增殖, 凋亡

Abstract: Objective To investigate the effect of triptolide (TP) on the proliferation and apoptosis of human non-small cell lung cancer cell A549 by regulating the expression of chemokine receptor 4 (CXCR4) gene. Methods The experiment was divided into 4 groups: control group, TP group (100 nm/L TP-treated cells), CXCR4+TP group (transfected plasmid TP-treated cells) and NC+TP group (empty plasmid TP-treated cells). The expression of CXCR4 and transfection were detected by RT-qPCR and Western blot. Cell proliferation was detected by MTT assay, apoptosis was detected by Annexin V-FITC/PI double staining, proliferation and apoptosis-related protein expression were detected by Western blot. Results Triptolide inhibited the expression of CXCR4 mRNA and protein in A549 cells (P＜0.05). Triptolide inhibited the proliferation of A549 cells and induced apoptosis(P＜0.05). Transfection of pcDNA-CXCR4 up-regulated the expression of CXCR4 mRNA and protein (P＜0.05). Up-regulation of CXCR4 expression partially reversed the effect of triptolide on proliferation inhibition and apoptosis induction of A549 cells (P＜0.05). Conclusions Triptolide may inhibit the proliferation of non-small cell lung cancer A549 cells and induce apoptosis by down-regulating the expression of CXCR4.

Key words: triptolide, CXCR4 gene, non-small cell lung cancer cell line A549, proliferation, apoptosis

中图分类号:

R730.23

刘倩, 汤建华, 张志华. 雷公藤甲素对非小细胞肺癌细胞系A549增殖的抑制和凋亡的诱导[J]. 基础医学与临床, 2020, 40(3): 315-320.

LIU Qian, TANG Jian-hua, ZHANG Zhi-hua. Triptolide inhibits the proliferation and promotes apoptosis of non-small cell lung cancer cell line A549[J]. Basic & Clinical Medicine, 2020, 40(3): 315-320.

参考文献

[1]Steendam CM, Dammeijer F, Jgjv A, et al. Immunotherapeutic strategies in non-small-cell lung cancer: the present and the future[J]. Immunotherapy, 2017, 9:507-520.
[2]Zhang B, Zhang Y, Yu D. Lung cancer gene therapy: Transferrin and hyaluronic acid dual ligand-decorated novel lipid carriers for targeted gene delivery[J]. Oncol Rep, 2017, 37:937-944.
[3]董智琦, 文国容, 庹必光. 趋化因子及其受体在肿瘤发生发展中作用的研究进展[J]. 安徽医药, 2018, 22:1011-1014.
[4]Tu Z, Xie S, Xiong M, et al. CXCR4 is involved in CD133-induced EMT in non-small cell lung cancer[J]. Int J Oncol, 2017, 50:505-514.
[5]Abraham M, Klein S, Bulvik B, et al. The CXCR4 inhibitor BL-8040 induces the apoptosis of AML blasts by down-regulating ERK BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression[J]. Leukemia, 2017, 31:2336-2346.
[6]陈茂剑, 肖潺潺, 王丽,等. 雷公藤甲素对乳腺癌MCF-7细胞增殖和凋亡的影响及其机制[J]. 实用医学杂志, 2017:3867-3870.
[7]赵东晓, 陈弘磊, 孟冠敏,等. 低浓度雷公藤甲素联合顺铂对肝癌细胞HepG2活性的影响[J]. 浙江中西医结合杂志, 2017, 27:366-369.
[8]Wang R, Ma X, Su S, et al. Triptolide antagonized the cisplatin resistance in human ovarian cancer cell line A2780/CP70 via hsa-mir-6751[J]. Future Med Chem, 2018, 10:1947-1955.
[9]Jiang C, Fang X, Zhang H, et al. Triptolide inhibits the growth of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and in vitro[J]. Tumour Biol, 2017, 39.doi:10.1177/1010428317697556.
[10]郑忠信, 柳约坚, 陈菲莉, 等. 低浓度雷公藤甲素联合伊达比星诱导急性髓系白血病干细胞凋亡及其机制[J]. 中山大学学报(医学科学版), 2014, 35:667-671.
[11]Zuo J, Wen M, Li S, et al. Overexpression of CXCR4 promotes invasion and migration of non-small cell lung cancer via EGFR and MMP-9[J]. Oncol Lett, 2017, 14:7513-7521.
[12]Bi MM, Shang B, Wang Z, et al. Expression of CXCR4 and VEGF-C is correlated with lymph node metastasis in non-small cell lung cancer[J]. Thoracic Cancer, 2017, 8:634-641.
[13]Li F, Zhao D, Yang S, et al. ITRAQ-based proteomics analysis of triptolide un human A549 lung adenocarcinoma cells[J]. Cell Physiol Biochem, 2018, 45:917-934.
[14]李英杰, 于长海, 李捷,等. PCNA和Ki-67在非小细胞肺癌组织中的表达及其临床意义[J]. 临床军医杂志, 2011, 39:261-263.
[15]Andreufernández V, Sancho M, Genovés A, et al. Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes[J]. Pro Natl Acad Sci U S A, 2017, 114:310-315.