Stichoposide C Exerts Anticancer Effects on Ovarian Cancer by Inducing Autophagy via Inhibiting AKT/mTOR Pathway.
Stichoposide C Exerts Anticancer Effects on Ovarian Cancer by Inducing Autophagy via Inhibiting AKT/mTOR Pathway.
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Stichoposide C 通过抑制 AKT/mTOR 通路诱导自噬对卵巢癌发挥抗癌作用
DOI：
10.2147/ott.s340556
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发表时间：
2022
影响因子：
4
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Liu F;Tang L;Tao M;Cui C;He D;Li L;Liao Y;Gao Y;He J;Sun F;Lin H;Li H
Stichoposide C（STC）是从菠萝参中分离得到的一种三萜苷类化合物，具有广谱的抗肿瘤活性。然而，卵巢癌（OC）细胞的抗肿瘤作用和潜在的分子机制尚未完全了解。在这里，我们研究了STC是否以及通过哪些机制对OC发挥抗癌作用。CCK-8和集落形成试验用于检测细胞活力和增殖。流式细胞仪检测细胞凋亡和细胞周期阻滞。蛋白质表达和磷酸化通过Western印迹分析测量。共聚焦荧光显微镜观察自噬通量。通过透射电子显微镜观察自噬体形成。在患者源性类器官（PDO）和A2780皮下异种移植肿瘤中研究了STC的抗肿瘤作用。STC不仅具有抗细胞增殖和诱导细胞凋亡的作用，而且还具有诱导自噬的作用。STC通过抑制卵巢癌细胞中的AKT/mTOR信号通路诱导自噬。此外，STC和自噬抑制剂3-甲基腺嘌呤（3-MA）联合处理在体外显示出显著的抑制增殖和促进凋亡的协同作用。与细胞实验一致，STC还抑制两种OC PDO的生长。最后，STC显着减少A2780皮下异种移植瘤的生长，而没有器官毒性和激活体内自噬。Stichoposide C通过抑制AKT/mTOR通路诱导自噬，发挥体内外抗卵巢癌作用。这些发现进一步证明STC作为卵巢癌的潜在治疗药物。
Stichoposide C (STC) is a triterpene glycoside isolated from Thelenota ananas, which is previously demonstrated to wide spectrum of anticancer effects against various tumor cells. However, the antitumor effects and underlying molecular mechanisms in ovarian cancer (OC) cells are not fully understood. Here, we examined if and through which mechanisms STC exerts anticancer effects on OC. CCK-8 and colony formation assays were used to detect cell viability and proliferation. Flow cytometry was used to detect apoptosis and cell cycle arrest. Protein expression and phosphorylation were measured by Western blotting analysis. Confocal fluorescence microscopy was used to observe the autophagy flux. Autophagosome formation was observed via transmission electron microscopy. Antitumor effect of STC was investigated in patient-derived organoids (PDOs) and A2780 subcutaneous xenograft tumors. STC was found that not only exerted antiproliferation activity and apoptosis but also induced autophagy. Mechanistically, STC induced autophagy via inhibited the AKT/mTOR signaling pathway in ovarian cancer cells. In addition, STC and an autophagy inhibitor 3-methyladenine (3-MA) combination treatment showed significant synergetic effects on inhibiting proliferation and promoting apoptosis in vitro. Consistent with cell experiments, STC also inhibited the growth of two OC PDOs. Finally, STC markedly reduced the growth of A2780 subcutaneous xenograft tumors without organ toxicity and activated autophagy in vivo. Stichoposide C exerts in vitro and in vivo anticancer effects on ovarian cancer by inducing autophagy via inhibiting AKT/mTOR pathway. The findings warrant further prove for STC as a potential therapeutic agent for ovarian cancer.
海参作为MDM2和CXCR4抑制剂的潜在使用以控制癌细胞的生长。
影响因子：
2.7
作者：
Wargasetia TL;Permana S;Widodo N
通讯作者：
Widodo N