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化合物YSY-01A是一种新合成的蛋白酶体抑制剂,前期研究已经证实其具有良好的抑制肿瘤增殖作用,但是其作用机制尤其是对细胞周期的阻滞作用仍不清楚。本实验旨在评价YSY-01A的抗肿瘤作用与细胞周期阻滞的关系,并探讨可能的分子机制。结果表明,YSY-01A能够显著抑制卵巢癌细胞SK-OV-3的增殖(P<0.05),且具有浓度和时间依赖性。进一步实验表明,YSY-01A能够引起SK-OV-3细胞G2/M周期阻滞,显著上调cyclin B1,cdc2和p-cdc2(T14)等蛋白的表达(P<0.05);YSY-01A亦可抑制由TNF-α引起的NF-κB核转位,同时上调IκBα、下调IKK和Gadd45α的表达水平。总之,YSY-01A对SK-OV-3细胞具有显著的增殖抑制作用,其分子机制与G2/M细胞周期阻滞有关。
YSY-01A is a newly synthesized proteasome inhibitor. Previous studies have shown that YSY-01A has a good inhibitory effect on tumor proliferation, but its mechanism of action, especially the cell cycle arrest, remains unclear. The purpose of this experiment was to evaluate the relationship between the anti-tumor effect of YSY-01A and cell cycle arrest and to explore possible molecular mechanisms. The results showed that YSY-01A could significantly inhibit the proliferation of ovarian cancer SK-OV-3 cells (P <0.05) in a concentration-and time-dependent manner. Further experiments showed that YSY-01A could induce G2 / M cycle arrest in SK-OV-3 cells and upregulate the expressions of cyclin B1, cdc2 and p-cdc2 (T14) (P <0.05) Inhibit nuclear translocation of NF-κB induced by TNF-α, upregulate IκBα and down-regulate the expression of IKK and Gadd45α. In summary, YSY-01A has a significant inhibitory effect on SK-OV-3 cells, and its molecular mechanism is related to G2 / M cell cycle arrest.