摘要
目的探讨选择性血管紧张素Ⅱ1型受体拮抗剂ZD7155在体外对胰腺癌细胞PaTu8988的抑制作用及其作用机制。方法采用四甲基偶氮唑盐(MTT)法测定浓度为5×10^(-11)、5×10^(-10)、5×10^(-9)、5×10^(-8)、5×10^(-7)和5×10^(-6)mol/L的ZD7155在同一时间点和5×10^(-8)mol/L ZD7155在不同作用时点对人胰腺癌细胞系PaTu8988的影响,应用流式细胞仪检测ZD7155作用前后PaTu8988细胞周期变化,电镜观察ZD7155对PaTu8988细胞凋亡的影响以及ZD7155对PaTu8988细胞形态的影响。结果MTT显示ZD7155的抑制率随着浓度增大、时间延长而增加。浓度分别为5×10^(-11)、5×10^(-10)、5×10^(-9)、5×10^(-8)、5×10^(-7)和5×10^(-6)mol/L的ZD7155在与PaTu8988细胞作用48h后。对其的抑制率分别为9%、18%、30%、51%、60%和78%。相同浓度(5.0×10^(-8)mol/L)的ZD7155在与PaTu8988作用后12、24、36、48、60和72h对其抑制率分别为15%、25%、36%、51%、67%和85%。ZD7155对人胰腺癌细胞系PaTu8988细胞周期S期有明显抑制作用,而且呈剂量依赖性。经与ZD7155共同孵育的细胞电镜下可见细胞核染色质边集、凋亡小体形成,而且随浓度升高而愈明显,细胞形态学未发生改变。结论ZD7155在体外能抑制胰腺癌细胞生长和增殖,其作用机制可能与其抑制细胞周期S期以及诱导细胞凋亡有关,且无明显细胞毒性作用。
Objective To investigate the effects and mechanisms of selective angiotensin Ⅱtype 1 receptor antagonist ZD7155 on the inhibition of pancreatic cancer in vitro. Methods MTT assays were used to determine the inhibition of pancreatic cancer cell line PaTu8988s by ZD7155 in different concentrations and at different time. PaTu8988s cell cycle and cell apoptosis were detected by flow cytometry. Transmission electron microscope was used to investigate the apoptosis of PaTu8988s before and after the incubation with ZD7155 under different concentrations. PaTu8988s cell morphology was observed before and after the incubation with ZD7155. Results MTT showed that the increase of inhibition of pancreatic cancer cell by ZD7155 was in agreement with the increase of the concentrations of ZD7155 and the time of the incubation with ZD7155. The inhibition rates of PaTu8988s cells were 9%, 18%, 30%, 51%, 60% and 78% by ZD7155 with the concentrations of 5 × 10^-11 , 5 × 10^-10 , 5 × 10^-9 , 5 × 10^-8 , 5 × 10^-7 and 5 × 10^-6 mol/L, respectively. The inhibition rates of PaTu8988s cells were 15%, 25%, 36%, 51%, 67% and 85% by ZD7155 with the same concentration(5.0 × 10^-8 mol/L) at 12, 24, 36, 48, 60 and 72 hours, respectively. ZD7155 could also inhibit PaTu8988s cell cycle significantly and was dose-dependent. Cell electron microscopy showed that there were chromatin margination and apoptotic body in the cell nucleus when the cells were incubated with ZD7155, and these changes were increase with the concentrations of ZD7155. The morphology of PaTu8988s cell didn't have any change after incubation with ZD7155. Conclusions ZD7155 can inhibit the growth of pancreatic cancer cells in vitro by suppressing the S-phase of cell cycle and induce cell apoptosis without visible cell toxic effects.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2007年第8期530-533,共4页
Chinese Journal of Digestion