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目的探讨温热化疗诱导不同分化程度胃癌细胞SGC7901和MKN45凋亡及其对凋亡调控基因表达的影响。方法体外培养中分化胃癌细胞SGC7901和低分化胃癌细胞MKN45并实施(43.0±0.1)℃温热化疗。用透射电子显微镜观察温热化疗后两种不同分化程度胃癌细胞的形态学改变。用末端原位标记法(TUNEL)测定肿瘤细胞的凋亡率。用流式细胞仪和Westernblot法分别测定凋亡调控基因Fas和bcl-2的表达水平。结果温热化疗诱导中分化胃癌细胞SGC7901凋亡的作用强于低分化胃癌细胞MKN45。温热化疗可诱导SGC7901凋亡调控基因Fas表达上调、bcl-2基因表达下调;但只诱导MKN45bcl-2基因表达下调,对MKN45Fas基因表达水平的影响不明显。结论温热化疗诱导分化较好的胃癌细胞的凋亡率大于低分化胃癌细胞;而Fas和bcl-2的表达水平可能是温热化疗后不同分化程度胃癌细胞凋亡率不同的重要原因。
Objective To investigate the effects of hyperthermic chemotherapy on the apoptosis of SGC7901 and MKN45 cells with different degrees of differentiation and their effects on the expression of apoptosis-controlling genes. Methods SGC7901 gastric cancer cells and MKN45 gastric cancer cells were cultured in vitro and treated with (43.0 ± 0.1) ℃ warm chemotherapy. Transmission electron microscopy was used to observe the morphological changes of two kinds of gastric cancer cells with different degrees of differentiation after thermotherapy. Tumor cell apoptosis rate was measured by TUNEL. The expression of Fas and bcl-2 genes were detected by flow cytometry and Western blot respectively. Results The apoptosis of SGC7901 cells induced by hyperthermia was stronger than that of poorly differentiated gastric cancer cells MKN45. The apoptosis of SGC7901 cells was induced by hyperthermic chemotherapy. The apoptosis of SGC7901 cells was up-regulated while the expression of bcl-2 gene was down-regulated. However, MKN45Fas gene expression was not significantly affected by down-regulation of MKN45bcl-2 gene expression. Conclusion The apoptosis rate of well differentiated gastric cancer cells induced by hyperthermal chemotherapy is higher than that of poorly differentiated gastric cancer cells. The expression of Fas and bcl-2 may be the reason of different apoptosis rates of gastric cancer cells with different degrees of differentiation after warm chemotherapy.