自交轴蛋白
癌症研究
癌症干细胞
转移
卵巢癌
活力测定
医学
紫杉醇
干细胞
细胞
癌症
内科学
化学
生物
受体
溶血磷脂酸
细胞生物学
生物化学
作者
JUN SE KIM,Min Joo Shin,Seo Yul Lee,SEONG MIN CHOI,Kyung Un Choi,Dong‐Soo Suh,DAE KYOUNG KIM,JAE HO KIM
出处
期刊:Anticancer Research
[Anticancer Research USA Inc.]
日期:2024-02-29
卷期号:44 (3): 1131-1142
被引量:1
标识
DOI:10.21873/anticanres.16908
摘要
Background/Aim: Cancer stem cells (CSCs) contribute significantly to the poor prognosis of patients with epithelial ovarian cancer (EOC) due to their roles in drug resistance and tumor metastasis. Autotaxin (ATX) plays a pivotal role in the maintenance of the CSC-like properties of EOC tumors. BBT-877 is a novel ATX inhibitor used in clinical treatment of idiopathic pulmonary fibrosis. However, the effects of BBT-877 on drug resistance and metastasis in ovarian CSCs remain unknown. In this study, we aimed to investigate the effects of BBT-877 on drug resistance and intraperitoneal metastasis of EOC. Materials and Methods: Spheroid-forming CSCs, which were isolated from two EOC cell lines, A2780 and SKOV3, were investigated by cell viability, western blot, PCR, Spheroid-forming assay, and in vivo experiments. Results: Spheroid-forming CSCs exhibited increased CSC-like properties and paclitaxel (PTX) resistance. BBT-877 treatment inhibited the viability of spheroid-forming CSCs more potently than that of adherent ovarian cancer cell lines. Combinatorial treatment with BBT-877 and PTX significantly attenuated the viability of spheroid-forming CSCs. In a SKOV3 cells-derived intraperitoneal metastasis model, BBT-877 treatment reduced the number of metastatic tumor nodes, while combinatorial treatment with BBT-877 and PTX more potently attenuated the formation of metastatic nodes and accumulation of ascitic fluid. Conclusion: These results suggest that BBT-877 can be combined with conventional anticancer drugs for the treatment of patients with recurrent or drug-resistant EOC.
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