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普罗卡布林在高级别浆液性卵巢癌细胞系模型中的抗肿瘤作用

Antitumoral Effect of Plocabulin in High Grade Serous Ovarian Carcinoma Cell Line Models.

作者信息

Heredia-Soto Victoria, Escudero Javier, Miguel María, Ruiz Patricia, Gallego Alejandro, Berjón Alberto, Hernández Alicia, Martínez-Díez Marta, Zheng Shuyu, Tang Jing, Hardisson David, Feliu Jaime, Redondo Andrés, Mendiola Marta

机构信息

Translational Oncology Research Laboratory, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.

Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.

出版信息

Front Oncol. 2022 Mar 17;12:862321. doi: 10.3389/fonc.2022.862321. eCollection 2022.

Abstract

Ovarian cancer (OC) is a life-threatening tumor and the deadliest among gynecological cancers in developed countries. First line treatment with a carboplatin/paclitaxel regime is initially effective in the majority of patients, but most advanced OC will recur and develop drug resistance. Therefore, the identification of alternative therapies is needed. In this study, we employed a panel of high-grade serous ovarian cancer (HGSOC) cell lines, in monolayer and three-dimensional cell cultures. We evaluated the effects of a novel tubulin-binding agent, plocabulin, on proliferation, cell cycle, migration and invasion. We have also tested combinations of plocabulin with several drugs currently used in OC in clinical practice. Our results show a potent antitumor activity of plocabulin, inhibiting proliferation, disrupting microtubule network, and decreasing their migration and invasion capabilities. We did not observe any synergistic combination of plocabulin with cisplatin, doxorubicin, gemcitabine or trabectedin. In conclusion, plocabulin has a potent antitumoral effect in HGSOC cell lines that warrants further clinical investigation.

摘要

卵巢癌(OC)是一种危及生命的肿瘤,在发达国家是妇科癌症中最致命的。采用卡铂/紫杉醇方案进行一线治疗最初对大多数患者有效,但大多数晚期OC会复发并产生耐药性。因此,需要确定替代疗法。在本研究中,我们使用了一组高级别浆液性卵巢癌(HGSOC)细胞系,进行单层和三维细胞培养。我们评估了一种新型微管蛋白结合剂普洛卡布啉对增殖、细胞周期、迁移和侵袭的影响。我们还测试了普洛卡布啉与几种目前在OC临床实践中使用的药物的联合使用情况。我们的结果显示普洛卡布啉具有强大的抗肿瘤活性,可抑制增殖、破坏微管网络并降低其迁移和侵袭能力。我们未观察到普洛卡布啉与顺铂、多柔比星、吉西他滨或曲贝替定有任何协同联合作用。总之,普洛卡布啉在HGSOC细胞系中具有强大的抗肿瘤作用,值得进一步进行临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b141/8969563/32c6b9b51a7c/fonc-12-862321-g001.jpg

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