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长生草碱抑制卵巢癌细胞的增殖、侵袭和转移,并在体内诱导超微结构变化。

Sempervirine inhibits proliferation, invasion and metastasis of ovarian cancer cells and induces ultrastructural changes in vivo.

作者信息

Chen Danni, Tan Yan, Chen Tingting, Wang Qin, Yan Yan, Zhao Xiaoya, Zhang Zhongxiao, Qiu Jin, Zhang Jian

机构信息

Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.

Department of Obstetrics and Gynecology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China.

出版信息

J Ovarian Res. 2025 Jan 28;18(1):17. doi: 10.1186/s13048-024-01580-4.

DOI:10.1186/s13048-024-01580-4
PMID:39875926
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11773766/
Abstract

Ovarian cancer is one of the deadliest gynecological malignancies due to its late diagnosis and easy recurrence. Therefore, it is urgent to develop novel therapeutics for ovarian cancer treatment. In this study, we evaluated the anti-ovarian cancer effects of sempervirine in vitro and in vivo. CCK8 assays showed that sempervirine dose-dependently inhibited the proliferation of SKOV3 ovarian cancer cells. Transwell assays demonstrated that sempervirine significantly suppressed the invasion and metastasis of SKOV3 cells. Furthermore, in an orthotopic ovarian cancer mouse model, sempervirine dramatically inhibited tumor growth and induced pathological changes in tumor tissues, including poor development of tumor mucosa, collagen deposition, endoplasmic reticulum damage, mitochondrial swelling and vacuolar degeneration, which were similar to the positive control 5-Fu. Mechanistic studies revealed that sempervirine decreased the expression of proteins related to apelin signaling pathway. In conclusion, our results demonstrate the potent anti-ovarian cancer effects of sempervirine both in vitro and in vivo. Sempervirine may repress ovarian cancer by down-regulating apelin signaling pathway. Our study suggests that sempervirine is a promising therapeutic agent against ovarian cancer.

摘要

卵巢癌是最致命的妇科恶性肿瘤之一,因其诊断较晚且易于复发。因此,开发用于治疗卵巢癌的新型疗法迫在眉睫。在本研究中,我们评估了蔓长春花碱在体外和体内对卵巢癌的抗癌作用。CCK8 试验表明,蔓长春花碱剂量依赖性地抑制 SKOV3 卵巢癌细胞的增殖。Transwell 试验证明,蔓长春花碱显著抑制 SKOV3 细胞的侵袭和转移。此外,在原位卵巢癌小鼠模型中,蔓长春花碱显著抑制肿瘤生长并诱导肿瘤组织发生病理变化,包括肿瘤黏膜发育不良、胶原沉积、内质网损伤、线粒体肿胀和空泡变性,这些与阳性对照 5-氟尿嘧啶相似。机制研究表明,蔓长春花碱降低了与阿片肽信号通路相关的蛋白质表达。总之,我们的结果证明了蔓长春花碱在体外和体内均具有强大的抗卵巢癌作用。蔓长春花碱可能通过下调阿片肽信号通路来抑制卵巢癌。我们的研究表明,蔓长春花碱是一种有前景的抗卵巢癌治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/d937cd644b89/13048_2024_1580_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/4e93b8238b6d/13048_2024_1580_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/0cd90c965061/13048_2024_1580_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/c595c109bb7c/13048_2024_1580_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/c00a1a3148c4/13048_2024_1580_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/963f8e7c6682/13048_2024_1580_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/d937cd644b89/13048_2024_1580_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/4e93b8238b6d/13048_2024_1580_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/0cd90c965061/13048_2024_1580_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/c595c109bb7c/13048_2024_1580_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/c00a1a3148c4/13048_2024_1580_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/963f8e7c6682/13048_2024_1580_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf26/11773766/d937cd644b89/13048_2024_1580_Fig6_HTML.jpg

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