PFT-α在调控热化疗损伤结肠上皮细胞增殖和周期中的作用

PFT-α regulates proliferation and cell cycle of large intestinal epithelial cells after hyperthermic chemotherapy injury

目的：探讨p53抑制剂PFT-α（p-fifty three inhibitor-alpha，PFT-α）对热化疗损伤肠上皮细胞增殖、周期的影响，及对热化疗损伤肠上皮细胞的保护作用。方法：MTT法分析PFT-α对结肠上皮细胞增殖及其对热化疗杀伤DLD1细胞的影响。顺铂联合温热处理结肠上皮细胞，对比加入不同浓度的PFT-α，Annexin V-FITC／PI和PI染色后流式细胞仪检测细胞凋亡和周期。结果：PFT-α在低于50μmol／L时，对于结肠上皮细胞增殖无影响，高于60μmol／L则抑制细胞增殖（P＜0．01）。PFT-α在5～40μmol／L之间。PFT-α不影响DLD1细胞生长，达50μmol／L时，则对肿瘤细胞的生长有一定的抑制效应（P〈0．05）。达60μmol／L，这种抑制效应更明显（P〈0．01）。PFT-α呈浓度依赖性降低热化疗诱导的结肠上皮细胞凋亡率，使细胞G2／M延长。结论：PFT-α可使细胞G2／M期延长而保护结肠上皮细胞。

Objective： To investigate the effects of PFT-α on the proliferation and cell cycle of large intestinal epithelial cells. The protective effects of PFT-α on cells was explored. Methods： The effects of PFT-α on proliferation of the large intestinal epithelial cells and the anti-tumor efficacy were observed by methabenzthiazuron （MTT） assay. The large intestinal epithelial cells were treated with hyperthermic （43℃） cisplatin （10 mg/L）, and in the absence or presence of PFT-α, the rate of apoptosis was detected by flow cytometry （FCM） with Annexin V - FITC and propidium iodide （PI） double labeling method. Cell cycle was analyzed by using FCM with PI labeling method. Results： PFT-α at the concentrations lower than 50 μM had no effect on the proliferation of large intestinal epithelial ceils, but PFT-α at the concentration of 60 μM could inhibit the growth of cells （P 〈 0.01）. PFT-α, ranging from 5 μM to 40 μM, had no effect on the growth of DLD1 cells, but could inhibit the growth of DLD1 cells when the concentrations were 50 μM （P 〈 0.05） and 60 μM （P 〈 0.01）, respectively. After treatment of large intestinal epithelial cells with different concentrations of PFT-α and thermochemotherapy, the apoptotic rate was decreased with the increasing concentrations. FCM analysis showed increased G2/M phase rate. Conclusion： PFT-α protects the large intestinal epithelial cells against hyperthermic chemotherapy injury through increasing G2/M phase rate.