糖原合成酶激酶3β对卵巢癌紫杉醇耐药性的影响及机制研究

摘要

Objective To study the effects of GSK-3βon paclitaxel chemoresistance of ovarian cancer cells .Methods SK-OV3 cells was treated with LiCl 20 mmol/L for 1 hour to enhance the expression of p-GSK-3β(ser9) which is inactivated.MTT was used to test the IC50 of paclitaxel.The expression of p-GSK-3β(ser9) was tested by FACS.The location of p-GSK-3β(ser9) in SK-OV3 cells was analyzed by immunofluorescence .Results After treated with LiCl, the IC50 of paclitaxel was increased from (10.11 ± 0.87) μg/mL to (11.56 ±0.96) μg/mL for 24 h, (1.07 ±0.17) μg/mL to (1.74 ±0.24) μg/mL for 48 h, (0.03 ±0.01)μg/mL to (0.06 ±0.01) μg/mL for 72 h respectively.Except the increase of 24 h others had statistical difference (P<0.05).FACS results show that the mean fluorescence intensity of p-GSK-3βincreased from (661.67 ±37.63) to (841.67 ±41.53) after treated with LiCl(P<0.05).The results of immunofluorescence show that the expression of p-GSK-3βin nuclear increased obviously than in the cytoplasm.Conclusion The augment of inactivated GSK-3βexpression, especially in the nuclear, can improve the chemoresis-tance of ovarian cancer cells .%目的：探讨糖原合成酶激酶3β（ GSK－3β）对卵巢癌紫杉醇耐药性的影响及机制。方法运用氯化锂（ LiCl ）增加卵巢癌细胞内失活性GSK－3β的表达，MTT法测定紫杉醇的半数抑制浓度（IC50），流式细胞仪检测p－GSK－3β（ser9）的表达量，免疫荧光观察其细胞内定位情况。结果 LiCl 20mmol／L处理1 h后，24、48、72 h SKOV3细胞紫杉醇的IC50从（10．11±0．87）、（1．07±0．17）、（0．03±0．01）μg／mL增加至（11．56±0．96）、（1．74±0．24）、（0．06±0．01）μg／mL，除24 h外差异均有统计学意义（P＜0．05）。 LiCl处理后SKOV3细胞内p－GSK－3β（ser9）的平均荧光强度由（661．67±37．63）增加到（841．67± 41．53），差异有统计学意义（P＜0．05）。 LiCl处理后SKOV3细胞核内p－GSK－3β（ser9）表达水平上调。结论 GSK－3β失活性磷酸化水平的增加，尤其是细胞核内表达水平的上调可导致卵巢癌细胞紫杉醇耐药性的增强。