千层纸素A通过PI3K/AKT信号通路诱导子宫内膜癌Ishikawa细胞株凋亡  

Oroxylin A induces apoptosis in Ishikawa cell line of endometrial cancervia PI3K/AKT signaling pathway

作　　者：赵焕焕[1] 焦煜茜 乔若琪 白雪[1] 王娜[1] 田芸婕 范文玲[1] 李利[1] 苏素文[3] 付炎[3] 张辉[1] 杨红芳[2] ZHAO Huan-huan;JIAO Yu-qian;QIAO Ruo-qi;BAI Xue;WANG Na;TIAN Yun-jie;FAN Wen-ling;LI Li;SU Su-wen;FU Yan;ZHANG Hui;YANG Hong-fang(Dept of Gynecology,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China;Dept of Laboratory Medicine,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China;Dept of Pharmacology,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学第四医院妇科,河北石家庄050011 [2]河北医科大学第四医院检验科,河北石家庄050011 [3]河北医科大学药理学教研室,河北石家庄050017

出　　处：《中国药理学通报》2025年第3期555-560,共6页Chinese Pharmacological Bulletin

基　　金：河北省中医药管理局项目(No 2021157)。

摘　　要：目的研究千层纸素A(oroxylin A,OA)对子宫内膜癌(endometrial cancer,EC)Ishikawa细胞凋亡的影响及其机制。方法用不同浓度的OA(0、4、8、10、12、20 mol·L^(-1))处理Ishikawa细胞,CCK-8法检测细胞活力,流式细胞术检测细胞凋亡,Western blot技术检测B细胞淋巴瘤/白血病-2基因(B-cell lymphoma-2,Bcl-2)、与Bcl-2同源的水溶性相关蛋白(Bcl-2-associated X protein,Bax)、PI3K/AKT、细胞色素P450家族成员1B1(recombinant cytochrome P4501B1,CYP1B1)、儿茶酚-O-甲基转移酶(catechol-O-methyltransferase,COMT)相关蛋白的表达水平。结果OA以剂量和时间依赖性方式抑制Ishikawa细胞的增殖;与空白对照组相比,随着OA浓度的升高,Bax蛋白表达明显增加,Bcl-2蛋白表达明显下降,COMT蛋白表达明显增加,CYP1B1蛋白表达明显下降。PI3K/AKT:补充IGF-1(PI3K激动剂)后出现逆转作用,COMT蛋白表达明显下降,CYP1B1蛋白表达明显增加。结论OA可抑制Ishikawa细胞的增殖,其机制与抑制P13K/AKT信号通路介导的凋亡有关。Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20μmol·L^(-1))for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P4501B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the proliferation of Ishikawa cells in a concentration-and time-dependent manner.Compared with the blank control group,the expression of Bax protein increased significantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significantly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3K agonist)supplementation reversed the effect,the expression of COMT protein significantly decreased,and the expression of CYP1B1 protein significantly increased.Conclusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

关 键 词：子宫内膜癌Ishikawa细胞 千层纸素A 凋亡 P13K/AKT CYP1B1 COMT 

分 类 号：R284.1[医药卫生—中药学] R329.25[医药卫生—中医学] R329.28R737.33R977.6