摘要
目的研究应用潘生丁(DP)阻断平衡型核苷转运载体(hENTs)后,5-氟尿嘧啶(5-FU)对胰腺癌细胞株Panc-1凋亡及细胞周期的影响。方法将Panc-1细胞分为hENTs未阻断组和hENTs阻断组,hENTs阻断组再根据DP浓度分为5μmol/L DP组和10μmol/L DP组。各组细胞分别在含有1.5×106ng/L 5-FU或不含5-FU的培养液中培养24 h后,流式细胞仪检测细胞的凋亡率和细胞周期改变。结果①各组细胞凋亡检测结果:在含有1.5×106ng/L 5-FU培养液中培养24 h后,5μmol/L及10μmol/L DP组的细胞凋亡率明显高于未阻断组(P<0.05),10μmol/L DP组又明显高于5μmol/L DP组(P<0.05);在不含5-FU的培养液中培养24 h后,各组之间细胞凋亡率比较差异无统计学意义(P>0.05)。②各组细胞周期检测结果:在含有1.5×106ng/L 5-FU培养液中培养24 h后,未阻断组细胞进入合成期(S期)的比例减少,停滞在合成前期(G1期),5μmol/L DP组及10μmol/L DP组的细胞进入合成期(S期)的比例较未阻断组进一步减少(P<0.05),且随着DP浓度的增加,细胞进入合成期(S期)的比例减少得更多(P<0.05),5μmol/L DP组和10μmol/L DP组进入合成期(S期)的比例分别是未阻断组的87.09%和74.06%。5-FU对细胞合成后期(G2期)的影响较小,除5μmol/L DP组较未阻断组G2期细胞数量增加有统计学意义(P<0.05)外,其余各组之间差异均无统计学意义(P>0.05);在不含5-FU的培养液中培养24 h后,各组细胞周期中各期无明显改变,各组之间比较差异均无统计学意义(P>0.05)。结论在胰腺癌细胞株Panc-1中,DP阻断细胞膜上hENTs后,能显著增强5-FU对胰腺癌细胞促凋亡作用及抑制胰腺癌细胞分裂增殖的作用,这种增强作用可能与阻断hENTs后细胞内5-FU浓度提高有关,而与DP本身作用无关。
Objective To investigate the effects of dipyridamole （DP）, one of the human equilibrative nucleo- side transporters （hENTs） blockers, on 5-fluorouracil （5-FU） induced cell apoptosis and cell cycle changes of the pancreatic cancer Pane-1 cell line. Methods Pancreatic cancer cell line Panc-1 was divided into hENTs blocked group and hENTs unblocked group. The hENTs blocked group was further divided into two subgroups according to the DP concentration, 5μmol/L DP group and 10μmol/L DP group. Each group was incubated in culture medium with or without 1.5×106 ng/L 5-FU for 24 h. Cell apoptosis and cell cycle were detected by flow cytometry. Re- sults ①The apoptosis results of each group= Incubated in culture medium with 1.5×10~ ng/L 5-FU for 24 h, the apoptosis rates of 5μmol/L DP group and 10 μmol/L DP group were higer than those of hENTs unblocked group （P〈0.05）, and which of 10μmol/L DP group was higer than that of 5μmol/L DP group （P〈0.05）. Incubated in culture medium without 5-FU for 24 h, there were no significant differences of the apoptosis rates among three groups （P〉0.05）. ②The cell cycle results of each group： Incubated in culture medium with 1.5×10^6 ng/L 5-FU for 24 h, the percentages of S phase cells in the 5 μmol/L DP group and 10μmol/L DP group were less than those of hENTs unblocked group （P〈0.05）. The percentage of S phase cell of 5μmol/L DP group reduced to 87.09%and that of 10μmol/L DP group reduced to 74.06% as compared with hENTs unblocked group. 5-FU had little in- fluence on G2 phase （P〉0.05） except for the percentage of G2 phase cells in the 5μmol/L DP group increased sig- nificantly （P〈0.05） as compared with the hENTs unblocked group. Incubated in culture medium without 5-FU for 24 h, there were no significant differences of the cell cycles among three groups （P〉0.05）. Conclusions In pancre- atic cancer Panc-1 cell, DP could enhance the cytotoxicity of 5-FU by blocking hENTs. The enhanced cytotoxicity is related to elevation of 5-FU concentration in cells, and unrelated to DP itself.
出处
《中国普外基础与临床杂志》
CAS
2011年第4期396-400,共5页
Chinese Journal of Bases and Clinics In General Surgery
