丙戊酸钠对人胰腺癌细胞PaTu8988增殖的影响及量效关系研究

Effect of valproic acid on the proliferation of human pancreatic cancer cell PaTu8988 and dose-effect relationship

目的探讨丙戊酸钠（VPA）对人胰腺癌PaTu8988细胞增殖和细胞周期的影响。方法应用0．2、1．0、5．0mmol／L的VPA干预人胰腺癌PaTu8988细胞24、48h，采用WST-8法检测细胞存活率，流式细胞仪检测细胞周期。以培养基中单加二甲基亚砜为空白对照组，单加PBS为PBS组。结果VPA干预24h后，VPA5．0mmol／L组的细胞生长抑制率为18．9％，显著高于对照组、PBS组及VPA0．2、1．0mmol／L组（0、4．4％、6．8％、6．i％，P值均〈0．05）；干预48h后，VPA1．0、5．0mmol／L组的细胞生长抑制率分别为12．9％、25．9％，显著高于对照组、PBS组、VPA0．2mmol／L组（0、6．2％、4．6％，P值均〈0．01）。VPA干预24h后，VPA1．0、5．0mmol／L组G2期细胞比例分别为（26．57±1．88）％、（34．11±4．74）％，显著高于PBS组、对照组、VPA0．2mmol／L组[（10．724±2．02）％、（13．53±2．28）％、（13．81±2．40）％，P值均〈0．01]；VPA干预48h后的细胞周期变化与24h一致。结论VPA呈时间及剂量依赖性抑制人胰腺癌PaTu8988细胞的增殖，诱导细胞阻滞在G2期。

Objective To investigate the effects of valproic acid （VPA） on cell proliferation and cell cycle in human pancreatic cancer cell line PaTu8988 in vitro. Methods PaTu8988 cells were treated with VPA in concentration of 0, 0.2, 1.0 or 5.0 mmol/L for 24 h and 48 h respectively. Cell viability was measured by WST-8 assay. Cell cycles were detected by flow cytometery. Dimethyl sulfoxide added to the medium was used as blank control group, while PBS added to the medium was used as PBS group. Results After VPA treatment for 24 h, the inhibition rate of VPA 5.0 mmol/L group was 18.9%, which was significantly higher than those in control group, PBS group and VPA 0.2, 1.0 mmol/L group （0, 4.4% , 6.8% , 6.1% , P 〈 0.05）. After 48 h, the inhibition rates of VPA 1.0, 5.0 mmol/L were 12.9% , 25.9% , which was significantly higher than those in control group, PBS group and VPA 0.2 mmol/L group （0, 6.2% , 4.6%, P 〈0.01）. After VPA treatment for 24 h, the proportions of G2 phase cell in VPA 1.0, 5.0 mmol/L group were （26.57 ±1.88） %, （34.11 ± 4.74） %, which was significantly higher than those in PBS group, control group, VPA 0.2 mmol/L group [（10.72±2.02）%, （13.53 ±2.28）%, （13.81 ±2.40）%, P 〈0.01 ], the changes 48 h after VPA treatment was consistent with the changes 24 h after VPA treatment. Conclusions VPA may significantly suppress the cell proliferation of human pancreatic cancer cell line PaTu8988, and induce cell cycle arrest in G2 phase in a time and dose-dependent manner.