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TGF-β1对胰腺癌细胞BxPC-3增殖的影响及机制 被引量：3

Growth-inhibition by TGF-β1 in BxPC-3 pancreatic carcinoma cell line and the primary mechanisms
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摘要 目的观察不同浓度梯度及不同时间梯度下外源性TGF-β1对胰腺癌细胞株BxPC-3增殖的影响,并探讨其可能的机制。方法以正常培养的BxPC-3细胞为空白对照,分别采用1.0、2.0、4.0、6.0、8.0ng/mL的TGF-β1干预BxPC-3细胞4d。MTT法观察各组胰腺癌细胞的生长情况,并计算肿瘤生长抑制率。同时以正常培养的BxPC-3细胞为对照组,以2.0ng/mL的TGF-β1分别干预BxPC-3细胞1～7d,MTT法绘制两组细胞生长曲线。另外,以2.0ng/mL的TGF-β1干预培养至第4天时分别采集两组细胞,用FCM检测细胞周期,Western blot方法检测细胞周期蛋白CyclinD1的表达。结果与空白对照组相比,TGF-β1干预组BxPC-3增殖受抑,并呈时间及浓度依赖。2.0ng/mL的TGF-β1干预组的最大生长抑制率为12.5%,出现在第4天;细胞周期阻滞在G1/S期;CyclinD1的蛋白表达也明显下调。结论外源性TGF-β1可轻度抑制Smad4纯合子缺失的BxPC-3胰腺癌细胞的生长,机制与细胞周期G/S阻滞及Cyclin D1下调有关。 Objective To observe the growth-inhibitory effect of TGF-β1 in BxPC-3 pancreatic carcinoma cell line and demonstrate its primary mechanisms involved.Methods To observe the dose-dependant manner,BxPC-3 pancreatic carcinoma cells were inoculated into the 96-well-plates.They were treated with 0,1.0,2.0,4.0,6.0 and 8.0 mg/L TGF-β1 respectively.MTT assay were performed after 4 days and the growth-inhibition rates were measured compared to the 0mg/L group as control.To observe the time-dependant manner,BxPC-3 cells were incubated with 2.0 mg/L TGF-β1 from 24 hours to 7 days,while the BxPC-3 cells without TGF-β1 incubation were considered as control.The growth curves were drawn in both groups with MTT assay.Meanwhile,cell cycle distribution was determined by flow cytometry after PI staining and Cyclin D1 expression was measured by Western blot assay in both control group and 2.0 mg/L TGF-β1 incubation group on the 4^th day.Results Compared with controls,BxPC-3 cells with 2 ng/mL TGF-β1 incubation for seven days caused a mild growth inhibition,and the maximal inhibitory rate was 12.5%,which was discovered on the 4th day.FCM analysis showed G1/S arrest of the cell cycle in TGF-β1-treated cells,while the CyclinD1 protein was also down-regulated significantly.Conclusions Although smad4 is depleted in BxPC-3 cells,exogenous TGF-β1 can still produce a mild growth inhibition in BxPC-3 pancreatic carcinoma cells,possibly through G1/S cell cycle arrest and Cyclin D1 down-regulation.
作者 钟良 陈坚 徐近 金忱 刘懿 张群华
机构地区 复旦大学附属华山医院消化科 复旦大学附属华山医院外科
出处 《复旦学报（医学版）》 CAS CSCD 北大核心 2008年第2期181-185,共5页 Fudan University Journal of Medical Sciences
关键词 胰腺癌 TGF-Β1 细胞周期 细胞周期蛋白D1 pancreatic carcinoma transforming growth factor beta cell cycle cyclin D1
分类号 Q253 [生物学—细胞生物学]
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参考文献17

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二级参考文献25

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复旦学报（医学版）
2008年 第2期

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