羟基红花黄色素A通过Wnt/β-catenin信号通路抑制卵巢癌生长

Hydroxysafflor Yellow A Inhibits Ovarian Cancer Growth through Wnt/β-catenin Signaling Pathway

目的研究羟基红花黄色素A(hydroxysafflor yellow A,HSYA)对卵巢癌的抑制作用及其机制。方法HSYA作用卵巢癌细胞株HO-8910PM 24h后,CCK-8法检测细胞增殖;流式细胞术检测细胞凋亡;Western blot法检测卵巢癌细胞中Nuclearβ-catenin、menin、MMP7、Survivin蛋白的表达;建立起裸鼠卵巢癌皮下移植瘤模型,免疫组织化学法检测肿瘤组织中menin、MMP7、Survivin阳性表达。结果与对照组比较,HSYA可明显抑制体外卵巢癌细胞生长,并诱导细胞凋亡;HSYA可抑制卵巢癌细胞Nuclearβ-catenin、MMP7、Survivin蛋白表达,而促进细胞内menin蛋白表达;体内实验中HSYA可显著抑制裸鼠卵巢癌皮下移植瘤生长,亦降低卵巢癌组织中MMP7、Survivin的阳性表达,但促进癌组织中menin阳性表达。结论HSYA可能通过促进menin表达,导致β-catenin降解,减少下游的癌基因MMP-7、Survivin表达,进而抑制卵巢癌细胞的生长,促进其凋亡。

Objective To explore the effect and the mechanism of HSYA in the growth inhibition of ovarian cancer.Methods After ovarian cancer cells HO-8910PM were treated with HSYA for 24h,cell growth was measured by the cell counting Kit-8(CCK-8)and apoptosis was evaluated by flow cytometry.The expression of Nuclearβ-catenin,menin,MMP7,Survivin in ovarian cancer cells was analyzed by Western blot assay.HO-8910PM cells were injected into nude mice to establish engrafted tumor model.Immunohistochemistry was used to detect the positive expression of menin,MMP7,Survivin in the ovarian tumors.Results Compared with the control group,HSYA could significantly inhibit the growth of ovarian cancer cells in vitro and induce apoptosis.HSYA can inhibit the expression of Nuclearβ-catenin,MMP7 and Survivin in ovarian cancer cells,and promote the expression of menin in cells.In vivo experiment HSYA can markly inhibit the growth of ovarian cancer transplanted subcutaneously in nude mice.After HSYA treatment,the positive expression of MMP7 and Survivin in ovarian cancer tissue decreased,while the expression of menin increased.Conclusion HSYA may inhibit the growth and promote apoptosis of ovarian cancer cells by promoting the expression of menin,leading to the degradation ofβ-catenin and reducing the expression of MMP-7 and Survivin.