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中国癌症防治杂志

中国癌症防治杂志 ›› 2019, Vol. 11 ›› Issue (3): 221-227.doi: 10.3969/j.issn.1674-5671.2019.03.08

• 基础研究 • 上一篇    下一篇

吡格列酮对人胰腺癌细胞株PANC-1增殖、凋亡的影响及分子机制研究

  

  1. 山东省淄博市第一医院药学部
  • 出版日期:2019-06-25 发布日期:2019-07-25

Effects of pioglitazone on proliferation and apoptosis of human pancreatic cancer cell line PANC-1 and its molecular mechanism

  • Online:2019-06-25 Published:2019-07-25

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摘要： 目的 探讨吡格列酮对人胰腺癌细胞株PANC-1增殖、凋亡的影响及其分子机制。方法 体外培养人胰腺癌细胞株PANC-1，分别以吡格列酮（0 μmol/L、10 μmol/L、20 μmol/L、50 μmol/L）和吉西他滨（50 μmol/L）作用0 h、12 h、24 h、48 h、72 h后，采用CCK-8检测各时间点的细胞增殖情况，流式细胞仪检测72 h细胞周期及凋亡情况，4，6-联脒-2-苯基吲哚（DAPI）染色检测48 h细胞凋亡形态学变化，Western blot检测48 h细胞凋亡相关蛋白及MAPK/ERK信号通路相关蛋白的表达。结果 与0 μmol/L吡格列酮相比，吉西他滨及各剂量吡格列酮组细胞作用24 h、48 h、72 h的OD值均降低（P＜0.05）；48 h 的G0/G1期细胞比例、细胞凋亡率、Bax及caspase-3、p-ERK蛋白表达均升高（P＜0.05），而S期细胞比例、Bcl-2蛋白表达降低（P＜0.05），且细胞逐渐收缩，细胞核逐渐碎裂。与50 μmol/L吉西他滨组相比，10 μmol/L吡格列酮组细胞作用24 h、48 h、72 h的OD值均升高（P＜0.05），而50 μmol/L吡格列酮组均降低（P＜0.05）；10 μmol/L吡格列酮组细胞作用48 h 的G0/G1期细胞比例、细胞凋亡率、Bax及caspase-3、p-ERK蛋白表达均降低（P＜0.05），而50 μmol/L吡格列酮组均升高（P＜0.05）；10 μmol/L吡格列酮组细胞48 h 的S期细胞比例、Bcl-2蛋白表达均升高（P＜0.05），而50 μmol/L吡格列酮组均降低（P＜0.05）。结论 吡格列酮能抑制人胰腺癌细胞株PANC-1增殖，诱导其凋亡，可能通过上调MAPK/ERK通路实现。

关键词: 胰腺癌, 吡格列酮, 增殖, 周期, 凋亡, PANC-1, MAPK/ERK通路

Abstract: Objective  To investigate the effects of pioglitazone on the proliferation and apoptosis of human pancreatic cancer cell line PANC-1 and its molecular mechanism. Methods Human pancreatic cancer cell line PANC-1 was cultured in vitro，pioglitazone （0，10，20，50 μmol/L） or gemcitabine（50 μmol/L） was administered for 0 h，12 h，24 h，48 h　and 72 h，respectively. The proliferation of PANC-1 cells was at 0 h，12 h，24 h，48 h and 72 h detected by CCK-8 assay，cell cycle，and apoptosis were detected by flow cytometry at 72 h，4，6-diamidino-2-phenylindole（DAPI） staining was used to detect the morphological changes of apoptosis at 48 h，Western blot was used to detect apoptosis and the expression of MAPK/ERK signaling pathway-related proteins at 48 h. Results Compared with pioglitazone at 0 μmol/L，OD value of PANC-1 cells in 50 μmol/L gemcitabine，10，20 and 50 μmol/L pioglitazone groups at 24 h，48 h and 72 h decreased significantly（P<0.05），and the percentage of G0/G1 phase cells，the apoptotic rate，the expressions of Bax and caspase-3、p-ERK proteins increased significantly at 48 h（P<0.05），while the proportion of S phase cells，the expressions of Bcl-2 protein decreased significantly（P<0.05） at 48 h，the degree of cell shrinkage gradually increased，and the nucleus gradually fragmented. Compared with the 50 μmol/L gemcitabine group，the OD values of PANC-1 cells in the 10 μmol/L pioglitazone group was increased（Ｐ＜0.05），while the 50 μmol/L pioglitazone group was decreased at 24 h，48 h and 72 h（P<0.05）；the proportion of G0/G1 cells，the apoptotic rate，the expressions of Bax and caspase-3,p-ERK proteins were decreased（P<0.05），while the 50 μmol/L pioglitazone group was increased at 48 h（P<0.05）；the proportion of cells in S phase，the expressions of Bcl-2 protein were increased（P<0.05），while the 50 μmol/L pioglitazone group was decreased at 48 h（P<0.05）. Conclusions Pioglitazone can inhibit the proliferation and induce apoptosis of pancreatic cancer cell PANC-1，and it may be achieved by up-regulating the MAPK/ERK pathway.

Key words: Pancreatic cancer；Pioglitazone；Proliferation；Cycle；Apoptosis；PANC-1；MAPK/ERK pathway 

中图分类号: 

  • R735.9