Koirala Kamal, Wan Yuan-lian, Liu Yu-cun, Wang Xin, Cui Wei, Wang Chun-lei, Chen Huan-nian, Wang Hui-yuan, Zhu Jing
Department of General Surgery, Peking University First Hospital, Beijinga100034, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Aug 18;38(4):385-8.
To investigate the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) in colon cancer cell lines and the effects of PPARgamma activation by its ligand troglitazone on cell growth in SW-480 cells.
PPARgamma expression was detected in Lovo, HT-29 and SW-480 cells using western blot. The effects of PPARgamma activation by its ligand troglitazone (TGZ) and selective antagonist T0070907 on cell growth were assessed by MTT and cell count methods; apoptosis was detected by flow cytometry method.
Western blot result revealed that PPARgamma protein was highly expressed in Lovo and HT-29 cells and there was relatively lower expression in SW-480 cells. Cell count method and MTT revealed that activation of SW-480 cells with TGZ resulted in inhibition of growth in a dose dependent manner. The effect of anti-proliferation increased with increasing doses of TGZ. Rates of growth inhibition were 3.3%, 8.3%, 25%, and 29% for different doses 5, 10, 20 and 25 micromol/L respectively. Flow cytometry method detected apoptosis in a dose-dependent manner. When the concentration of TGZ was less than 15 micromol/L , the apoptotic effect was found to be weak. The apoptotic effect was prominent when the concentration exceeded 20 micromol/L. Cell count method revealed that selective antagonist of PPARgamma stimulated cell growth of SW-480 cells in a dose dependent manner.
PPARgamma is expressed in colon cancer cells. Activation of PPARgamma by its ligands in colon cells has potent anti-proliferative and pro-apoptotic effects, suggesting that PPARgamma activation by its ligands may provide therapeutic value for colorectal cancer patients.
研究过氧化物酶体增殖物激活受体γ(PPARγ)在结肠癌细胞系中的表达,以及其配体曲格列酮激活PPARγ对SW - 480细胞生长的影响。
采用蛋白质免疫印迹法检测Lovo、HT - 29和SW - 480细胞中PPARγ的表达。通过MTT法和细胞计数法评估其配体曲格列酮(TGZ)和选择性拮抗剂T0070907激活PPARγ对细胞生长的影响;采用流式细胞术检测细胞凋亡。
蛋白质免疫印迹结果显示,PPARγ蛋白在Lovo和HT - 29细胞中高表达,在SW - 480细胞中表达相对较低。细胞计数法和MTT法显示,用TGZ激活SW - 480细胞可导致其生长呈剂量依赖性抑制。抗增殖作用随TGZ剂量增加而增强。不同剂量5、10、20和25 μmol/L时的生长抑制率分别为3.3%、8.3%、25%和29%。流式细胞术检测到细胞凋亡呈剂量依赖性。当TGZ浓度小于15 μmol/L时,凋亡作用较弱。当浓度超过20 μmol/L时,凋亡作用显著。细胞计数法显示,PPARγ的选择性拮抗剂可剂量依赖性地刺激SW - 480细胞生长。
PPARγ在结肠癌细胞中表达。其配体激活结肠细胞中的PPARγ具有强大的抗增殖和促凋亡作用,提示其配体激活PPARγ可能为结直肠癌患者提供治疗价值。