卡铂联合TRAIL对肺癌A549细胞增殖和凋亡的影响

doi:10.3969/j.issn.1004-616x.2015.02.007

癌变·畸变·突变 ›› 2015, Vol. 27 ›› Issue (2): 111-115.doi: 10.3969/j.issn.1004-616x.2015.02.007

卡铂联合TRAIL对肺癌A549细胞增殖和凋亡的影响

王慧敏¹, 王宏英¹, 戴素丽², 李磊², 赵连梅²

1. 内蒙古赤峰市医院呼吸内科, 内蒙古赤峰 024300;
2. 河北医科大学第四医院科研中心, 河北石家庄 050011

收稿日期:2014-09-10 修回日期:2014-12-08 出版日期:2015-03-31 发布日期:2015-03-31
通讯作者: 赵连梅,E-mail:lianmeizhmail@163.com E-mail:lianmeizhmail@163.com
作者简介:王慧敏,E-mail:huimin-wang@126.com。
基金资助:
河北省卫生厅医学科学研究重点课题项目(20120120)

Effects of carboplatin combination with TRAIL on the proliferation and apoptosis of lung adenocarcinoma cancer cell line A549

WANG Huimin¹, WANG Hongying¹, DAI Suli², LI Lei², ZHAO Lianmei²

1. Department of Respiratory Medicine, Chifeng Municipal Hospital, Chifeng 024300, Inner Mongolia;
2. Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China

Received:2014-09-10 Revised:2014-12-08 Online:2015-03-31 Published:2015-03-31
About author:10.3969/j.issn.1004-616x.2015.02.007

摘要/Abstract

摘要：

目的:观察卡铂联合TNF相关凋亡诱导配体(TRAIL)对人肺腺癌细胞A549增殖和凋亡的影响。方法:经20、40、80 μg/mL卡铂和100 ng/μL TRAIL单用或联用处理后,用MTS法检测A549细胞的增殖能力,在光镜下观察细胞形态学变化;并采用流式细胞术检测细胞凋亡情况;RT-PCR和Western blot法检测死亡受体4(DR4)、死亡受体5(DR5)、Survivin和X连锁凋亡抑制蛋白基因(XIAP)mRNA与蛋白表达的变化。结果:卡铂和TRAIL单用或联用均可浓度依赖性抑制A549细胞的增殖,诱导其凋亡,两药联用比单用卡铂时抑制率和凋亡率更高(P<0.05)。单用卡铂或TRAIL可使A549细胞数减少,漂浮细胞增多,出现明显的凋亡形态变化,且明显降低Survivin和XIAP的mRNA和蛋白表达水平(P均<0.05);但对A549细胞DR4和DR5 mRNA表达均无明显影响,而单用卡铂或TRAIL却能升高A549细胞DR5蛋白的表达(P<0.05)。与单用组相比,TRAIL与卡铂联用A549细胞凋亡形态变化更明显,可明显降低A549细胞Survivin和XIAP mRNA和蛋白的表达水平及升高DR5蛋白表达水平(P<0.05)。结论:卡铂与TRAIL联用可协同抑制肺癌细胞A549细胞增殖,促进其凋亡,且与卡铂能够增加A549细胞DR5蛋白的表达和降低Survivin及XIAP的表达相关。

关键词: 卡铂, TNF相关凋亡诱导配体, A549, 增殖, 凋亡

Abstract:

OBJECTIVE:To study the effects of carboplatin combined with TRAIL (TNF- related apoptosis inducing ligand) on proliferation and apoptosis of human lung cancer A549 cells. METHODS:After treated by TRAIL, carboplatin or combination of two drugs, the proliferation of A549 was measured by MTS and apoptosis rate was evaluated by flow cytometry. The morphology was investigated by microscopy. RT-PCR and Western blot were used to examine the gene and protein expressions of DR4, DR5, Survivin and XIAP. RESULTS:Carboplatin or TRAIL alone or combined inhibited the proliferation of A549 cells in concentration-dependent (20-80 μg/mL) manner. Carboplatin combined with TRAIL exhibited a stronger inhibitory effect and induced apoptosis than when used alone. Carboplatin could down-regulate the protein expression level of Survivin and XIAP and increase the DR5 protein expression level, but have no effect on DR4 expression. CONCLUSION:Combination of carboplatin and TRAIL could inhibit proliferation and apoptosis via influencing the expressions of Survivin, XIAP and DR5 in A549 cells.

Key words: carboplatin, TRAIL, A549, proliferation, apoptosis

中图分类号:

R730.2

王慧敏, 王宏英, 戴素丽, 李磊, 赵连梅. 卡铂联合TRAIL对肺癌A549细胞增殖和凋亡的影响[J]. 癌变·畸变·突变, 2015, 27(2): 111-115.

WANG Huimin, WANG Hongying, DAI Suli, LI Lei, ZHAO Lianmei. Effects of carboplatin combination with TRAIL on the proliferation and apoptosis of lung adenocarcinoma cancer cell line A549[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2015, 27(2): 111-115.

参考文献

[1] 陈万青, 张思维, 邹小农. 中国肺癌发病死亡的估计和流行趋势研究[J]. 中国肺癌杂志, 2010, 13 (5):488-493.
[2] Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer[J]. N Engl J Med, 2006, 355(24):2542-2550.
[3] Takayama K, Inoue K, Tokunaga S, et al. Phase II study of concurrent thoracic radiotherapy in combination with weekly paclitaxel plus carboplatin in locally advanced non-small cell lung cancer:LOGIK0401[J]. Cancer Chemoth Pharm, 2013, 72(6):1353-1359.
[4] Schneider PD, Olson A, Tardivel B, et al. Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)[J]. J Biol Chem, 2003, 278(7):5444-5454.
[5] Matsuzaki H, Schmied BM, Ulrich A, et al. Combination of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) and actinomycin D induces apoptosis even in TRAIL- resistant human pancreatic cancer cells[J]. Clin Cancer Res, 2001, 7(2):407-414.
[6] Hwang H, Biswas R, Chung PS, et al. Modulation of EGFR and ROS induced cytochrome c release by combination of photodynamic therapy and carboplatin in human cultured head and neck cancer cells and tumor xenograft in nude mice[J]. J Photoch Photobiol B, 2013, 128(1):70-77.
[7] Mahalingam D, Szegezdi E, Keane M, et al. TRAIL receptor signalling and modulation:Are we on the right TRAIL[J]. Cancer Treat Rev, 2009, 35(3):280-288.
[8] Maduro JH, Noordhuis MG, ten Hoor KA, et al. The prognostic value of TRAIL and its death receptors in cervical cancer[J]. Int J Radiat Oncol Biol Phys, 2009, 75(1):203-211.
[9] 孙非凡, 孙铭娟, 王梁华, 等. TRAIL联合吉西他滨对肺癌NCI-H460细胞增殖和凋亡的影响[J]. 中国肿瘤生物治疗杂志, 2011, l (3):296-300.
[10] Zhai G, Kim H, Sarver D, et al. Early therapy assessment of combined anti-DR5 antibody and carboplatin in triple-negative breast cancer xenografts in mice using diffusion-weighted imaging and 1H MR spectroscopy[J]. J Magn Reson Imaging, 2014, 39(6):1588-1594.
[11] Deveraux QL, Takahashi R, Salvesen GS, et al. X-linked IAP is a direct inhibitor of cell-death proteases[J]. Nature, 1997, 388 (6639):300-304.
[12] Truneh A, Sharma S, Silverman C, et al. Temperature-sensitive differential affinity of TRAIL for its receptors DR5 is the highest affinity receptor[J]. J Biol Chem, 2000, 275(30): 23319 -23325.

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卡铂联合TRAIL对肺癌A549细胞增殖和凋亡的影响

Effects of carboplatin combination with TRAIL on the proliferation and apoptosis of lung adenocarcinoma cancer cell line A549

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