苯乙酸对胰腺癌细胞DNA合成的抑制作用

Inhibitory effect of phenylacetate on DNA synthesis of pancreatic cancer cells

目的:观察苯乙酸(PA)对胰腺癌细胞BXPC-3的增殖抑制作用,并在分子水平上探讨其作用机制。方法:通过细胞计数及MTT法检测不同剂量(0、0.25、0.50、1.00、2.00和4.00 mmol·L-1)PA对胰腺癌细胞BXPC-3的增殖抑制作用,通过流式细胞术(FCM)分析各细胞周期的细胞百分比。结果:BXPC-3细胞分别经0.25、0.50、1.00、2.00和4.00 mmol·L-1PA作用72 h后,增殖抑制率分别为31.0%±1.6%、54.8%±1.2%、68.3%±2.4%、79.9%±2.1%和81.1%±1.3%,均明显高于阴性对照组(1.2%±0.2%)(P<0.05),且0.25、0.50、1.00和2.00 mmol·L-1PA各组间细胞增殖抑制率均随PA浓度增加而明显增高(P<0.05),但2.00与4.00 mmol.L-1PA组间细胞增殖抑制率比较差异无统计学意义(P>0.05)。FCM分析BXPC-3细胞周期变化,经1.00 mmol·L-1PA作用72 h后G0/G1期比例由61.8%下降至51.3%,G2+M期比例由9.4%下降至9.2%;经2.00 mmol·L-1PA作用72 h后G0/G1期比例由61.8%下降至32.3%,G2+M期比例由9.4%下降至8.1%。2.00 mmol.L-1PA组与未用药组间比较差异有统计学意义(P<0.05)。结论:PA可阻抑细胞增殖周期于G1期,减少DNA合成,抑制细胞增殖,作用机制为PA抑制BXPC-3细胞周期中G1期的某种效应蛋白RNA的功能表达。

Objective To investigate the inhibitory effect of phenylacetate（PA） on cell proliferation of pancreatic cancer cells and to study the mechanism of the effect at the molecular level.Methods The inhibitory effects of different doses of PA（0,0.25,0.50,1.00,2.00 and 4.00 mmol·L-1） on pancreatic cancer cells BXPC-3 were detected by MTT and cell numeration methods.The cell percentages in different cell cycles were tested by flow cytometry（FCM）.Results After treated with different concentrations（0.25,0.50,1.00,2.00 and 4.00 mmol·L-1） of PA for 72 h,the inhibitory rates of proliferation of BXPC-3 cells（31.0%±1.6%,54.8%±1.2%,68.3%±2.4%,79.9%±2.1%,81.1%±1.3%,respectively） were much higher than that in control group（1.2%±0.2%）（P0.05）.With the increasing of concentrations from 0.25 to 2.00 mmol·L-1,the inhibitory rates of proliferation were significantly increased （P0.05）,but there was no significant difference between 2.00 and 4.00 mmol·L-1 PA groups（P0.05）.The FCM result showed that the ratio of G0/G1 phase of BXPC-3 cells after treated with 1.0 mmol·L-1 PA for 72 h was decreased from 61.8% to 51.3%,the ratio of G2＋M phase from 9.4% to 9.2%;the ratio of G0/G1 phase of BXPC-3 cells after treated with 2.0 mmol·L-1 PA 72 h was decreased from 61.8% to 32.3%,the ratio of G2＋M phase from 9.4% to 8.1%,the difference between 2.00 mmol·L-1 PA and control group was significant（P0.05）.Conclusion PA can supress the cell cycle at G1 phase,and decrease the DNA synthesis,and inhibit the cell proliferation.The mechanism is that PA can inhibit the RNA expressions of some kinds of proteins in G1 phase in BXPC3 cells.