蛋白酶体抑制剂MG132对人子宫内膜癌HEC-1B和Ishikawa细胞增殖、凋亡和周期的影响

【摘要】 目的 了解蛋白酶体抑制剂三肽基乙醛（Z-Leu-Leu-Leu-cho, MG132）抗人子宫内膜癌HEC-1B和Ishikawa细胞的活性，研究MG132治疗人子宫内膜癌的潜在应用价值。方法 用不同浓度的MG132(0，0.2，0.5，1.0 μmol/L)处理HEC-1B和Ishikawa细胞24 h、48 h，采用MTT法检测MG132对HEC-1B和Ishikawa细胞增殖的影响；应用流式细胞术分别检测0.5 μmol/L MG132处理24 h后两种细胞的凋亡率和细胞周期分布。结果 MG132能抑制HEC-1B和Ishikawa细胞增殖，在本研究浓度范围内MG132浓度增高对两种细胞的抑制作用增强（P<0.01），48 h抑制作用强于24 h(P<0.01)，Ishikawa细胞对MG132的敏感程度大于HEC-1B细胞。MG132处理HEC-1B和Ishikawa细胞后凋亡率均增加（P=0.000），细胞周期分析显示HEC-1B细胞G2期细胞比例增加（P<0.05），Ishikawa细胞G1和G2细胞比例增加（P<0.05）。结论 蛋白酶体抑制剂MG132对HEC-1B和Ishikawa细胞有增殖抑制、诱导凋亡和阻滞细胞周期的作用。MG132可能成为潜在的子宫内膜癌化疗药物。

Effects of Proteasome Inhibitor MG132 on Cell Proliferation, Apoptosis, and Cell Cycle in HEC-1B and Ishikawa Cells

【Abstract】 Objective To study the anti-cancer activities of Z-Leu-Leu-Leu-cho (MG132) against human endometrial carcinoma HEC-1B and Ishikawa cells and the potential of MG132 in human endometrial cancer therapy. Methods HEC-1B and Ishikawa cells were treated with MG132. Cell proliferation was assessed by MTT while cell apoptosis rate and cell-cycle distribution were assessed by flow cytometry. Results The proliferation of HEC-1B and Ishikawa cells was inhibited by MG132 and cell proliferation was significantly inhibited with the raised concentration of MG132 (P<0.01), Ishikawa cells were more sensitive than HEC-1B cells to MG132. MG132 could induce the apoptosis of HEC-1B and Ishikawa cells (P=0.000). Cell cycle analysis indicated that the percentage of HEC-1B cells was increased in G2 phase (P<0.05) while Ishikawa cells’ was increased in G1 and G2 phase (P<0.05). Conclusion Proteasome inhibitor MGl32 could inhibit the proliferation, promote cell apoptosis, and block the cell cycle of HEC-1B and Ishikawa cells. MG132 may be a potential treatment for endometrial cancer.