塞来昔布联合放疗对人胆管癌细胞凋亡的作用研究
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摘要
目的研究人胆管癌细胞在塞来昔布和放疗作用下发生凋亡的作用机制。方法将QBC939细胞株分为四组:对照组、塞来昔布组(C组)、放疗组(R组)和塞来昔布联合放疗组(C+R组,联合组),分别进行不同浓度的塞来昔布和不同剂量X线作用后,采用CCK-8法、流式细胞技术和Western blot等方法分别检测各组细胞生长、凋亡率及survivin蛋白的表达。结果联合组的凋亡率明显增加,从3.527%升至23.364%(P<0.05),survivin蛋白表达明显降低(P<0.05)。结论应用塞来昔布对接受放疗的人QBC939细胞株有凋亡增敏作用,下调survivin的表达是其机制之一。
Objective To investigate the effect of celecoxib in combination with radiotherapy on the apoptosis of human cholangiocarcinoma cell line QBC939 in vitro. Methods The QBC939 cells were maintained in RIMP1640 supplemented with 10% FBS and treated with celecoxib in combination with x-ray. Cell Counting Kit-8(CCK-8)assay was used to investigate the inhibition ratio and the IC50. Cells were divided into four groups including control, radiotherapy,celecoxib, radiotherapy and celecoxib. Apoptosis of each group was determined by flow cytometry. Expression of survivin was determined by western blot. Results The apoptosis ratio of the combination treatment groups were enhanced apparently, from 3.527% of control group to 23.364%(P<0.05). Survivin expression was down-regulated obviously after combination treatment in western blot. Conclusion Celecoxib could enhance radiotherapy's effect of apoptosis-inducing. Celecoxib has the radiosensitivity-enchancing effect on the cholangiocarcinoma QBC939 cells in vitro, down regulation of survivin expression may be one of the possible mechanisms.
Objective To investigate the effect of celecoxib in combination with radiotherapy on the apoptosis of human cholangiocarcinoma cell line QBC939 in vitro. Methods The QBC939 cells were maintained in RIMP1640 supplemented with 10% FBS and treated with celecoxib in combination with x-ray. Cell Counting Kit-8(CCK-8)assay was used to investigate the inhibition ratio and the IC50. Cells were divided into four groups including control, radiotherapy,celecoxib, radiotherapy and celecoxib. Apoptosis of each group was determined by flow cytometry. Expression of survivin was determined by western blot. Results The apoptosis ratio of the combination treatment groups were enhanced apparently, from 3.527% of control group to 23.364%(P<0.05). Survivin expression was down-regulated obviously after combination treatment in western blot. Conclusion Celecoxib could enhance radiotherapy's effect of apoptosis-inducing. Celecoxib has the radiosensitivity-enchancing effect on the cholangiocarcinoma QBC939 cells in vitro, down regulation of survivin expression may be one of the possible mechanisms.
引文
[1]许燕艳,翟凤钰,王亚帝,等.塞来昔布联合多西他赛抑制人乳腺癌MDA-MB-231细胞增殖和诱导凋亡的作用研究[J].中国全科医学,2013,16(3):1004-1007.
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[10]王瞡,庞义存,赵向寨.survivin基因在绒毛膜癌细胞中的表达及对细胞增殖、凋亡的影响[J].中华妇产科杂志,2014,49(6):466-468.
[11]王平,董德平,张建平.下调survivin基因对膀胱尿路上皮癌T24细胞增生和凋亡的影响[J].中华实验外科杂志,2013,30(12):2521-2524.
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[13]李伟忠,王晓燕,霍秋菊.塞来昔布对人舌鳞癌Tca8113细胞survivin表达与诱导细胞凋亡的作用[J].广东医学杂志,2010,31(5):543-545.
[14]方雷,吴海滨,陈晓岗.Survivin基因沉默抑制胃癌MGC-803细胞增殖并增强其对塞来昔布的敏感性[J].南方医科大学学报,2011,31(11):1944-1948.
[15]Bai XM,Jiang H,Ding JX,et al.Prostaglandin E2 upregulates survivin expression via the EP1 receptor in hepatocellular carcinoma cells[J].Life Sciences,2010,(86):214-223.
[2]周任,张龙洲,王睿智.塞来昔布对胶质瘤U251细胞增殖、凋亡和Survivin表达的影响[J].癌症,2010,29(3):316-322.
[3]牛国梁,王辉,谢荣俊,等.选择性COX-2抑制剂塞来昔布对乳腺癌的放疗增敏作用及其机制研究[J].肿瘤学杂志,2011,17(3):172-176.
[4]周海存,刘宏斌.塞来昔布防治胃癌的机制及应用前景[J].中华消化外科杂志,2013,(4):317-320.
[5]Davis TW,O'Neal JM,Pagel MD,et al.Synergy between celecoxib and radiotherapy results from inhibition of cyclooxygenase-2-derived prostaglandin E2,a survival factor for tumor and associated vasculature[J].Cancer Res,2004,64(1):279-285.
[6]Milas L.Cyclooxygenase-2(COX-2)enzyme inhibitors and radiotherapy:Preclinical basis[J].Am J Clin Oncol,2003,26(4):66-69.
[7]聂亮琴,周菊英,王利利.塞来昔布对正常脑胶质细胞和脑胶质瘤细胞放射增敏效应的比较及其机制[J].中华放射医学与防护杂志,2014,34(5):342-344,375.
[8]卢浩,刘士维,张伟.凋亡抑制因子Survivin的研究进展[J].山东医药,2014,54(21):100-101.
[9]朱正明,欧阳喜,罗洪亮,等.Survivin基因启动子区多态性与结肠癌易感性及临床意义的相关性[J].世界华人消化杂志,2014,22(9):1334-1340.
[10]王瞡,庞义存,赵向寨.survivin基因在绒毛膜癌细胞中的表达及对细胞增殖、凋亡的影响[J].中华妇产科杂志,2014,49(6):466-468.
[11]王平,董德平,张建平.下调survivin基因对膀胱尿路上皮癌T24细胞增生和凋亡的影响[J].中华实验外科杂志,2013,30(12):2521-2524.
[12]夏历,谢小兵,宁兴旺.Survivin和COX-2在胃癌组织中的表达及其相关性[J].现代生物医学进展,2010,10(10):1916-1919.
[13]李伟忠,王晓燕,霍秋菊.塞来昔布对人舌鳞癌Tca8113细胞survivin表达与诱导细胞凋亡的作用[J].广东医学杂志,2010,31(5):543-545.
[14]方雷,吴海滨,陈晓岗.Survivin基因沉默抑制胃癌MGC-803细胞增殖并增强其对塞来昔布的敏感性[J].南方医科大学学报,2011,31(11):1944-1948.
[15]Bai XM,Jiang H,Ding JX,et al.Prostaglandin E2 upregulates survivin expression via the EP1 receptor in hepatocellular carcinoma cells[J].Life Sciences,2010,(86):214-223.