>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
藤黄酸对顺铂诱导A549/DDP细胞凋亡的增敏作用
作者:许露1  朱晓莉2  王欢2  韩淑华2  黄亭亭1 
单位:1. 东南大学 医学院, 江苏 南京 210009;
2. 东南大学附属中大医院 呼吸科, 江苏 南京 210009
关键词:藤黄酸 非小细胞肺癌 顺铂 耐药 细胞凋亡 P-糖蛋白 
分类号:R734.2;R979.1
出版年·卷·期(页码):2019·38·第三期(438-444)
摘要:

目的:探讨藤黄酸(GA)是否能作为肺癌化疗中顺铂(DDP)的增敏剂。方法:采用细胞增殖试验和等辐射分析法研究DDP联合GA对非小细胞肺癌耐药株A549/DDP的抑制作用,并测定其对B淋巴细胞瘤-2(Bcl-2)和P-糖蛋白(P-gp)表达的影响。结果:GA可显著增强A549/DDP细胞对DDP介导的细胞凋亡的敏感性,显著增加DDP诱导细胞的早期凋亡(20.58±5.68)%、晚期凋亡(17.47±4.05)%和G2/M期停滞(44.13±3.78)%。GA与DDP联合组中,P-gp及抗凋亡蛋白Bcl-2被显著抑制(P=0.006及P=0.007),促凋亡蛋白Bax显著增加(P=0.006)。此外,联合治疗也抑制了p53蛋白(P<0.01)的表达。结论:GA通过增加DDP在细胞内积聚和增强DDP介导的DDP耐药肺癌细胞凋亡来增强DDP的作用,GA可以作为DDP诱导A549/DDP细胞凋亡的良好增敏剂,但其潜在的机制尚待进一步探明。

Objective:To determine whether gambogic acid(GA) is a sensitizer for cisplatin(DDP) in chemotherapy of lung cancer. Methods:Cell proliferation test and other radiation analysis were used to study the inhibitory effect of DDP combined with GA on A549/DDP, and to determine its effect on the expression of B-cell lymphoma-2(Bcl-2) and p-glycoprotein(P-gp). Results:GA could significantly enhance the sensitivity of A549/DDP cells to apoptosis induced by DDP. It significantly increased the early apoptosis(20.58±5.68)%, late apoptosis(17.47±4.05)% and G2/M-stage stagnation(44.13±3.78)% induced by cisplatin. In the combined group of GA and DDP, the P-gp and anti-apoptotic protein Bcl-2 were significantly inhibited(P=0.006), and pro-apoptotic protein Bcl-2 associated X protein(Bax)(P=0.006) increased significantly. In addition, combined treatment also inhibited the expression of p53 protein(P<0.01). Conclusion:GA can enhance the effect of cisplatin by increasing the accumulation of DDP in cells and enhancing the apoptosis induced by cisplatin in cisplatin-resistant no small cell lung cancer cells,and GA is a good sensitizer for the apoptosis of A549/DDP cells induced by DDP. But its potential mechanisms need to be further elaborated.

参考文献:

[1] SIEGEL R L,MILLER K D,JEMAL A.Cancer statistics,2015[J].CA Cancer J Clin,2015,65(1):5-29.
[2] AZZOLI C G,TEMIN S,ALIFF T,et al.2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage Ⅳ non-small-cell lung cancer[J].J Clin Oncol,2011,29(28):3825-3831.
[3] ETTINGER D S,WOOD D E,AKERLEY W,et al.Non-small cell lung cancer,version 6.2015[J].J Natl Compr Canc Netw,2015,13(5):515-524.
[4] AZZOLI C G,TEMIN S,GIACCONE G.2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage Ⅳ non-small-cell lung cancer[J].J Oncol Pract,2012,8(1):63-66.
[5] ZHAO T,WANG H J,ZHAO W W,et al.Gambogic acid improves non-small cell lung cancer progression by inhibition of mTOR signaling pathway[J].Kaohsiung J Med Sci,2017,33(11):543-549.
[6] ZHANG H Z,KASIBHATLA S,WANG Y,et al.Discovery,characterization and SAR of gambogic acid as a potent apoptosis inducer by a HTS assay[J].Bioorg Med Chem,2004,12(2):309-317.
[7] CHEN Q,YU Q,LIU Y,et al.Multifunctional selenium nanoparticles:chiral selectivity of delivering MDR-siRNA for reversal of multidrug resistance and real-time biofluorescence imaging[J].Nanomedicine,2015,11(7):1773-1784.
[8] YANG L,SHI T,LIU F,et al.REV3L,a promising target in regulating the chemosensitivity of cervical cancer cells[J].PLoS One,2015,10(3):334-352.
[9] MIRANDA H F,PUIG M M,PRIETO J C,et al.Synergism between paracetamol and nonsteroidal anti-inflammatory drugs in experimental acute pain[J].Pain,2006,121(1-2):22-28.
[10] HUANG J,ZHU X,WANG H,et al.Role of gambogic acid and NaI131 in A549/DDP cells[J].Oncol Lett,2017,13(1):37-44.
[11] CHEN P M,CHENG Y W,WU T C,et al.MnSOD overexpression confers cisplatin resistance in lung adenocarcinoma via the NF-κB/Snail/Bcl-2 pathway[J].Free Radic Biol Med,2015,79:127-137.
[12] WU D W,WU T C,WU J Y,et al.Phosphorylation of paxillin confers cisplatin resistance in non-small cell lung cancer via activating ERK-mediated Bcl-2 expression[J].Oncogene,2014,33(35):4385-4395.
[13] NISHIOKA T,LUO L Y,SHEN L,et al.Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability[J].Br J Cancer,2014,110(7):1785-1792.
[14] LAN D,WANG L,HE R,et al.Exogenous glutathione contributes to cisplatin resistance in lung cancer A549 cells[J].Am J Transl Res,2018,10(5):1295-1309.
[15] CHEN Y L,YANG T Y,CHEN K C,et al.Hypoxia can impair doxorubicin resistance of non-small cell lung cancer cells by inhibiting MRP1 and P-gp expression and boosting the chemosensitizing effects of MRP1 and P-gp blockers[J].Cell Oncol(Dordr),2016,39(5):411-433.
[16] LEO M,GOMES S,PEDRAZA-CHAVERRI J,et al.A mangostin and gambogic acid as potential inhibitors of the p53-MDM2 interaction revealed by a yeast approach[J].J Nat Prod,2013,76(4):774-778.
[17] KOSTER R,TIMMER-BOSSCHA H,BISCHOFF R,et al.Disruption of the MDM2-p53 interaction strongly potentiates p53-dependent apoptosis in cisplatin-resistant human testicular carcinoma cells via the Fas/FasL pathway[J].Cell Death Dis,2011,2:148-159.
[18] TANG X,HU G,XU C,et al.HZ08 reverse the aneuploidy-induced cisplatin-resistance in Gastric cancer by modulating the p53 pathway[J].Eur J Pharmacol,2013,720(1-3):84-97.
[19] CHEE J L,SAIDIN S,LANE D P,et al.Wild-type and mutant p53 mediate cisplatin resistance through interaction and inhibition of active caspase-9[J].Cell Cycle,2013,12(2):278-288.
[20] SARIN N,ENGEL F,KALAYDA G V,et al.Cisplatin resistance in non-small cell lung cancer cells is associated with an abrogation of cisplatin-induced G2/M cell cycle arrest[J].PLoS One,2017,12(7):81-99.
[21] GADHIKAR M A,SCIUTO M R,ALVES M V,et al.Chk1/2 inhibition overcomes the cisplatin resistance of head and neck cancer cells secondary to the loss of functional p53[J].Mol Cancer Ther,2013,12(9):1860-1873.
[22] 郭晓彤,魏优蕾,雷加吉,等.藤黄酸对非小细胞肺癌A549细胞凋亡及Bcl-2、Bax、P53基因表达的影响[J].中国老年学杂志,2018,38(4):911-914.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 180378 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364