低剂量LBH589通过PI3K/AKT途径诱导对上皮性卵巢癌细胞凋亡作用机制研究

朱静; 宋悦

doi:10.13898/j.cnki.issn.1000-2200.2019.06.003

低剂量LBH589通过PI3K/AKT途径诱导对上皮性卵巢癌细胞凋亡作用机制研究

朱静,
宋悦

Study on the mechanism of apoptosis induced by low-dose LBH 589 through PI3K/AKT pathway in epithelial ovarian cancer cells

ZHU Jing,
SONG Yue

摘要

摘要:
目的探讨低剂量LBH589通过PI3K/AKT途径诱导对上皮性卵巢癌细胞凋亡作用机制的影响。
方法以上皮性卵巢癌细胞OVCAR-3为研究对象，使用TUNEL和流式细胞术，分别检测添加（实验组）与不添加（对照组）低剂量LBH589上皮性卵巢癌细胞的细胞凋亡情况与周期变化；MTT法检测低剂量LBH589对上皮性卵巢癌细胞增殖的抑制情况；Western blotting检测2组中PI3K和AKT表达情况以及其磷酸化的情况。
结果实验组细胞凋亡指数明显高于对照组的（3.86±1.26）%（P < 0.01），上皮性卵巢癌细胞S期数量（18.27±1.66）%，明显低于对照组的（42.26±1.35）%（P < 0.01），实验组12、24、36、48 h抑制率分别为（12.35±0.27）%、（21.24±0.33）%、（33.54±0.26）%、（41.23±0.52）%，对照组抑制率始终为0；实验组的EOC细胞对顺铂的敏感性显著增加（P < 0.01），逆转系数是对照组的3.26倍，明显抑制PI3K和AKT在卵巢癌细胞中的表达并抑制其磷酸化（P < 0.01）。
结论低剂量LBH589能增加上皮性卵巢癌细胞OVCAR-3的凋亡，并可能通过PI3K/AKT通路逆转顺铂耐药。

Abstract:
ObjectiveTo investigate the effects of low-dose LBH589 on the apoptosis of epithelial ovarian cancer cells induced by PI3K/AKT pathway.
MethodsThe apoptosis and cycle of epithelial ovarian cancer cells(OVCAR-3 cells) in the experimental group with low-dose LBH589 inducing and control group without low-dose LBH589 inducing were detected using TUNEL and flow cytometry, respectively.The inhibition of low-dose LBH589 on epithelial overian cancer cell proliferation was detected using MTT assay, and the expression levels of PI3K, AKT p-PI3K and p-AKT in two groups were detected using Western blot ting.
ResultsThe cell apoptosis index in experimental group was significantly higher than that in control group(P < 0.01), the number of epithelial ovarian cancer cells in S-phase in experimental group was significantly lower than that in control group(P < 0.01).The inhibitory rates of epithelial ovarian cancer cells in experimental group at 12, 24, 36 and 48 h were(12.35±0.27)%, (21.24±0.33)%, (33.54±0.26)% and(41.23±0.52)%, respectively.The inhibition rate in control group was 0.In experimental group, the sensitivity of EOC cells to cisplatin significantly increased(P < 0.01), and the reversal coefficient was 3.26 times of control group.Compared with the control group, the expression levels of PI3K, AKT, p-PI3K and p-AKT in ovarian cancer cells were significantly inhibited in experimental group(P < 0.01).
ConclusionsThe low-dose LBH589 can increase the apoptosis of the epithelial ovarian cancer cells OVCAR-3, and may reverse the cisplatin resistance through the PI3K/AKT pathway.

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