[1]谢燕,喻秀丽,童立纺.硼替佐米对A549细胞增殖及p21、p27表达的影响[J].第三军医大学学报,2012,34(17):1775-1778.
 Xie Yan,Yu Xiuli,Tong Lifang.Anti-proliferation effect of proteasome inhibitor bortezomib in human lung adenocarcinoma A549 cells[J].J Third Mil Med Univ,2012,34(17):1775-1778.
点击复制

硼替佐米对A549细胞增殖及p21、p27表达的影响(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
34卷
期数:
2012年第17期
页码:
1775-1778
栏目:
论著
出版日期:
2012-09-15

文章信息/Info

Title:
Anti-proliferation effect of proteasome inhibitor bortezomib in human lung adenocarcinoma A549 cells
作者:
谢燕喻秀丽童立纺
重庆医科大学附属第一医院青杠老年护养中心
Author(s):
Xie Yan Yu Xiuli Tong Lifang
Department of Qinggang Geriatrics, Frist Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China
关键词:
硼替佐米肺癌细胞周期
Keywords:
bortezomib lung cancer cell cycle
分类号:
R73-361; R730.23; R734.2
文献标志码:
A
摘要:
目的      研究蛋白酶体抑制剂硼替佐米对人肺癌A549细胞增殖、细胞周期及在体成瘤的影响。      方法       采用不同浓度的硼替佐米(0、100、200 nmol/L)作用于A549细胞4 h,观察其对蛋白酶体活性的影响。用硼替佐米(0、100、200 nmol/L)处理A549细胞48 h,采用MTT法、3H-TdR掺入法检测细胞增殖;流式细胞术PI染色检测细胞周期;Western blot检测p21、p27表达水平的变化;连续注射观察硼替佐米对裸鼠A549细胞移植瘤体积及质量的影响。      结果       硼替佐米可显著抑制A549细胞的蛋白酶体活性。MTT法、3H-TdR法检测显示,100 nmol/L处理组细胞较对照组增殖率分别降低24.5%、29.5%,200 nmol/L处理组进一步显著下降(P<0.05);细胞周期分析显示,100、200 nmol/L处理组G0/G1期较对照组明显增加(P<0.05)。Western blot检测显示,48 h时100、200 nmol/L处理组p21、p27蛋白表达较对照组明显增加,且呈浓度依赖(P<0.05),48 h蛋白质水平高于24 h。连续注射硼替佐米后裸鼠移植瘤的质量抑制率达(36.0±12.4)%。      结论       硼替佐米可抑制A549细胞增殖,诱导细胞凋亡及发生G0/G1期阻滞,在体注射可抑制裸鼠成瘤,其抗肿瘤活性可能与抑制细胞周期蛋白p21、p27的降解有关。
Abstract:
Objective       To investigate the effects of a proteasome inhibitor bortezomib on the proliferation, cell cycle and tumor formation of human lung adenocarcinoma A549 cells, and to explore the possible mechanisms involved.       Methods       Human lung adenocarcinoma A549 cells were cultured and treated with different concentrations of bortezomib (0, 100 and 200 nmol/L) for 4 h, and the proteasome activity were measured to confirm its inhibitory effects. The A549 cells were further treated with different concentrations of bortezomib (0, 100 and 200 nmol/L) for 24-48 h. Cell proliferation was determined by MTT assay and 3H-TdR absorption, respectively. Cell cycle was detected by flow cytometry, and the protein levels of p21 and p27 were determined by Western blotting. A549 cells were implanted subcutaneously into nude mice to establish the xenograft tumor models, and the xenograft tumor bearing mice were subjected to bortezomib. The tumor volume and weight in all groups were measured, and the tumor inhibitory rate was calculated.       Results       Bortezomib significantly inhibited the proteasome activity in A549 cells. The MTT and 3H-TdR results showed that cell proliferation decreased by 24.5% and 29.5% in the 100 nmol/L bortezomib group, respectively, and a more significant decease was observed in the 200 nmol/L bortezomib group compared with the control group (P<0.05). Cell cycle analysis showed that the number of cells at G0/G1 phase was significantly increased in the 100 nmol/L and 200 nmol/L bortezomib groups compared with the control group (P<0.05). Western blot results showed that p21 and p27 significantly increased in a dose-dependent manner in the 100 nmol/L and 200 nmol/L bortezomib groups compared with the control group (P<0.05). In addition, the levels of p21 and p27 in the bortezomib group were significantly higher at 48 h than those at 24 h. After continuous injection, the weight of the xenograft tumors was reduced by (36.0±12.4)% in the bortezomib group compared with the control group.       Conclusion       Bortezomib can inhibit A549 cell proliferation and induce cell cycle arresting at G0/G1phase, probably by inhibiting the degradation of p21 and p27 proteins in A549 cells.

参考文献/References:

谢燕, 喻秀丽, 童立纺. 硼替佐米对A549细胞增殖及p21、p27表达的影响[J].第三军医大学学报,2012,34(17):1775-1778.

相似文献/References:

[1]王孟昭,张紫萱.肺癌的靶向治疗[J].第三军医大学学报,2012,34(20):2035.
 Wang Mengzhao,Zhang Zixuan.Target therapy in lung cancer[J].J Third Mil Med Univ,2012,34(17):2035.
[2]莫贵艳,李敏,胡成平,等.茶氨酸对内皮细胞生长及肺癌血管生成的影响[J].第三军医大学学报,2012,34(20):2043.
 Mo Guiyan,Li Min,Hu Chengping,et al.Theanine suppresses angiogenesis of endothelial cells in vitro and in vivo[J].J Third Mil Med Univ,2012,34(17):2043.
[3]刘晓丽,马礼鸿,王全义,等.XIAP、c-jun在肺癌组织中的表达及其意义[J].第三军医大学学报,2012,34(23):2408.
 Liu Xiaoli,Ma Lihong,Wang Quanyi,et al.Expression and clinical significance of XIAP and c-jun in human lung cancer tissues[J].J Third Mil Med Univ,2012,34(17):2408.
[4]李佳丽,刘耀,曾东风,等.硼替佐米联合地塞米松和沙利度胺治疗多发性骨髓瘤的临床研究[J].第三军医大学学报,2012,34(24):2515.
 Li Jiali,Liu Yao,Zeng Dongfeng,et al.Bortezomib combined with dexamethasone and thalidomide in treatment of multiple myeloma: report of 58 cases[J].J Third Mil Med Univ,2012,34(17):2515.
[5]李长毅,张明川,梅同华,等.持续小剂量化疗对A549肺癌PTEN基因和凋亡的影响[J].第三军医大学学报,2007,29(18):1760.
 LI Chang-yi,ZHANG Ming-chuan,MEI Tong-hua,et al.Low-dose metronomic chemotherapy upregulates PTEN and induces apoptosis of A549 pulmonary adenocarcinoma in athymic mice[J].J Third Mil Med Univ,2007,29(17):1760.
[6]邓丽平,董文,杜艳萍,等.支气管肺泡灌洗液和血清肿瘤标志物联合检测在肺癌诊断中的价值[J].第三军医大学学报,2008,30(01):78.
 DENG Li-ping,DONG Wen,DU Yan-ping,et al.Combined determination of tumor markers in serum and bronchoalveolar lavage fluid for lung cancer diagnosis[J].J Third Mil Med Univ,2008,30(17):78.
[7]李代蓉,周清华,郭占林,等.CYP2E1基因多态性与肺癌遗传易感性的关系[J].第三军医大学学报,2008,30(13):1231.
 LI Dai-rong,ZHOU Qing-hua,GUO Zhan-lin,et al.Association between genetic polymorphisms of CYP2E1 and lung cancer susceptibility: a case control study[J].J Third Mil Med Univ,2008,30(17):1231.
[8]李艳秋,李建春,关洪全,等.肺癌患者外周血Th1/Th2细胞因子及IL-18水平变化与肿瘤分期的关系[J].第三军医大学学报,2007,29(08):731.
 LI Yan-qiu,LI Jian-chun,GUAN Hong-quan,et al.Changes of IL-18 and Th1/Th2 in serum of lung cancer patients and their relationship with tumor staging[J].J Third Mil Med Univ,2007,29(17):731.
[9]戴纪刚,肖颖彬,闵家新,等.非小细胞肺癌线粒体基因组大片段缺失突变研究[J].第三军医大学学报,2006,28(21):2123.
[10]王红梅,廖国清,雷红,等.晚期肺癌患者肺部感染病原学分析[J].第三军医大学学报,2006,28(20):2103.

更新日期/Last Update: 2012-08-31