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岩藻甾醇通过诱导线粒体介导的凋亡、抑制细胞周期迁移以及下调m-TOR/PI3K/Akt信号通路,对人宫颈癌HeLa细胞系表现出选择性抗肿瘤抗癌活性。

Fucosterol exhibits selective antitumor anticancer activity against HeLa human cervical cell line by inducing mitochondrial mediated apoptosis, cell cycle migration inhibition and downregulation of m-TOR/PI3K/Akt signalling pathway.

作者信息

Jiang Hongye, Li Jie, Chen Aiyue, Li Yinguang, Xia Meng, Guo Peng, Yao Shuzhong, Chen Shuqin

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510086, P.R. China.

出版信息

Oncol Lett. 2018 Mar;15(3):3458-3463. doi: 10.3892/ol.2018.7769. Epub 2018 Jan 10.

Abstract

Cervical cancer greatly contributes to cancer-associated mortalities worldwide. The growing incidence of cervical cancer is of primary concern, and has signaled the need for multiple treatment options. Despite preliminary responses to chemotherapy and/or surgical interventions, the tumors consistently relapse. Previously, natural products gained attention for their diverse bioactivities, which include however are not limited to, neuroprotective, antimicrobial and anticancer effects. The present study evaluated the anticancer activity of fucosterol against a panel of human cancer cell lines. Results indicated that fucosterol exhibited selective inhibitory activity against human HeLa cervical cancer cell line with an IC of 40 µM. Fucosterol also induced apoptosis in HeLa cells and prompted reactive oxygen species mediated alterations in mitochondrial membrane potential. It triggered cell cycle arrest of HeLa cells at G2/M check point and exerted inhibitory effects on cell migration. The activation of the phosphoinositide-3-kinase (PI3K)/AKT Serine/Threonine Kinase 1 (AKT)/mechanistic target of Rapamycin (mTOR) pathway is important in cancer tumorigenesis, progression and chemotherapy resistance. The results demonstrated that fucosterol significantly inhibited the expression levels of key proteins of the PI3K/Akt/mTOR signaling pathway. Overall, the results of the present study suggest that fucosterol may prove beneficial in the management of cervical cancer.

摘要

宫颈癌在全球癌症相关死亡率中占很大比例。宫颈癌发病率的不断上升是首要关注的问题,这表明需要多种治疗选择。尽管对化疗和/或手术干预有初步反应,但肿瘤仍持续复发。此前,天然产物因其多样的生物活性而受到关注,这些生物活性包括但不限于神经保护、抗菌和抗癌作用。本研究评估了岩藻甾醇对一组人类癌细胞系的抗癌活性。结果表明,岩藻甾醇对人宫颈癌HeLa细胞系表现出选择性抑制活性,半数抑制浓度为40µM。岩藻甾醇还诱导HeLa细胞凋亡,并促使活性氧介导线粒体膜电位改变。它引发HeLa细胞在G2/M检查点的细胞周期停滞,并对细胞迁移产生抑制作用。磷酸肌醇-3-激酶(PI3K)/AKT丝氨酸/苏氨酸激酶1(AKT)/雷帕霉素靶蛋白(mTOR)信号通路的激活在癌症肿瘤发生、发展和化疗耐药中起重要作用。结果表明,岩藻甾醇显著抑制PI3K/Akt/mTOR信号通路关键蛋白的表达水平。总体而言,本研究结果表明岩藻甾醇可能对宫颈癌的治疗有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1fe/5795881/d60bf5c3a3e8/ol-15-03-3458-g00.jpg

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