TSA诱导胰腺癌BxPC-3细胞周期阻滞与凋亡的研究  

Induction of cell cycle arrest and apoptosis in BxPC-3 human pancreatic cancer cells by trichostatin A

作　　者：张世能[1] 蔡霞[2] 徐凤琴[1] 张亚雷[1] 黄志清[1] 曾志勇[1] 

机构地区：[1]中山大学附属第二医院消化内科,广东广州510120 [2]广州医学院附属肿瘤医院,广东广州510095

出　　处：《中华肿瘤防治杂志》2007年第7期525-528,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：广东省自然科学基金(04009381)

摘　　要：目的观察曲古抑菌素A(tricho-statin A,TSA)对胰腺癌BxPC-3细胞增殖及凋亡的诱导作用,探讨TSA抗胰腺癌的作用机制。方法BxPC-3细胞应用TSA处理后采用流式细胞技术分析其细胞周期分布和细胞凋亡率,免疫组化方法检测细胞乙酰化组蛋白H4表达,Western blot分析p21 WAF1/CIP1蛋白表达。结果TSA对胰腺癌BxPC-3细胞具有生长抑制作用,且呈时间和剂量依赖性。TSA可将BxPC-3细胞阻滞于G0/G1期,TSA组G0/G1期细胞达(61.8±2.5)%,较空白对照组(42.5±2.2)%和乙醇对照组(47.3±3.4)%明显增多(P=0.004);三组细胞凋亡率分别为25.5%、5.5%和5.1%(P=0.000)。TSA组细胞p21 WAF1/CIP1蛋白表达及其相关染色质乙酰化组蛋白H4表达上调。结论TSA对胰腺癌BxPC-3细胞增殖和细胞周期具有影响作用并可诱导细胞凋亡,p21 WAF1/CIP1蛋白及其相关染色质乙酰化组蛋白H4表达上调可能是其抗胰腺癌作用机制之一。OBJECTIVE：To investigate the effect and its mechanism of trichostatin A（TSA） on inhibition of cell proliferation and induction of apoptosis in BxPC-3 human pancreatic cancer cells. METHODS：A human pancreatic cancer cell line BxPC-3 was treated with TSA. The cell cycle status and apoptosis were carried out by flow cytometry . Expression of acetylated histone H4 was determined with the immunocytochemical assay.Expression of p21 WAF1/CIP1 was detected by Western blotting. RESULTS：TSA significantly inhibited the proliferation of BxPC-3 human pancreatic cancer cells in a time-and dose-dependent manner. BxPC 3 cells treated with TSA was arrested in G0/G1 phase. Compared with the blank control group （42.5 ± 2.2）% and ethanol group （47.3 ± 3.4）% ,TSA group （61.8 ± 2.5 ）% was significantly increased （P= 0. 004）. The apoptosis rate of BxPC-3 cell was markedly enhanced in TSA group （25.5%） compared with the blank control group （5.5%） and ethanol group （5. 1%）,P=0.000. The expressions of acetylated histone H4, p21 WAF1/CIP1 were significantly increased after being treated with TSA. CONCLUSIONS：The results suggest that TSA may inhibit pancreatic cancer cell growth in vitro, and in duee cell cycle arrest and the apoptosis rate of BxPC 3 human pan creatic cancer cell. TSA acts as an anti cancer agent by up regulating the expressions of acetylated histone H4 and p21 WAF1/CIP1.

关 键 词：抗肿瘤药/药理学 胰腺肿瘤/病理学 细胞周期 细胞凋亡/药物作用 免疫组织化学 

分 类 号：R735.9[医药卫生—肿瘤]