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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 inhibitory effect of selective angiotensin Ⅱ type 1 receptor antagonist ZD7155 on pancreatic cancer cell line PaTu8988 and its mechanism. Methods MTT assay was used to determine the concentration of 5 × 10 ~ (-11), 5 × 10 ~ (-10), 5 × 10 ~ (-9), 5 × 10 ~ (-8) ), 5 × 10 ~ (-7) and 5 × 10 ~ (-6) mol / L of ZD7155 at the same time point and 5 × 10 ~ (-8) mol / L of ZD7155 at different time points on human pancreatic cancer Cell line PaTu8988. The cell cycle of PaTu8988 cells was detected by flow cytometry before and after ZD7155 treatment. The effect of ZD7155 on apoptosis of PaTu8988 cells and the effect of ZD7155 on the morphology of PaTu8988 cells were observed by electron microscope. Results MTT showed that the inhibition rate of ZD7155 increased with the increase of concentration and time. The concentrations of 5 × 10 ~ (-11), 5 × 10 ~ (-10), 5 × 10 ~ (-9), 5 × 10 ~ (-8), 5 × 10 ~ (-7) After treated with 10 ~ (-6) mol / L ZD7155 for 48h, the cells were treated with PaTu8988. Its inhibition rates were 9%, 18%, 30%, 51%, 60% and 78% respectively. The inhibition rate of ZD7155 at the same concentration (5.0 × 10 -8 mol / L) was 15%, 25%, 36% and 51% at 12, 24, 36, 48, 60 and 72h after treated with PaTu8988, , 67% and 85% respectively. ZD7155 inhibited the cell cycle S phase of human pancreatic cancer cell line PaTu8988 in a dose-dependent manner. After incubation with ZD7155 cells under the electron microscope, the nucleus chromatin margins and apoptotic bodies formed, and the more obvious with the increase of concentration, the cell morphology did not change. Conclusion ZD7155 can inhibit the growth and proliferation of pancreatic cancer cells in vitro, and its mechanism may be related to its inhibition of S phase of cell cycle and induction of apoptosis, and no obvious cytotoxicity.