Department of Gynecology, Zibo Central Hospital, No. 54 of Gongqingtuan West Road, Zhangdian District, Zibo 255000, Shandong, China.
Department of Reproductive Medicine, Binzhou Medical University Hospital, No. 661 of Huanghe 2 Road, Binzhou 256600, Shandong, China.
J Biochem. 2021 Sep 7;169(6):747-756. doi: 10.1093/jb/mvab021.
Paclitaxel (PTX) is the standard first-line treatment of ovarian cancer, but its efficacy is limited by multidrug resistance. Therefore, it is crucial to identify effective drug targets to facilitate PTX sensitivity for ovarian cancer treatment. Seventy PTX-administrated ovarian cancer patients were recruited in this study for gene expression and survival rate analyses. Muscleblind-like-3 (MBNL3) gain-of-function and loss-of-function experiments were carried out in ovarian cancer cells (parental and PTX-resistant) and xenograft model. Cancer cell viability, apoptosis, spheroids formation, Nanog gene silencing were examined and conducted to dissect the underlying mechanism of MBNL3-mediated PTX resistance. High expression of MBNL3 was positively correlated with PTX resistance and poor prognosis of ovarian cancer. MBNL3 increased cell viability and decreased apoptosis in ovarian stem-like cells, through upregulating Nanog. This study suggests the MBNL3-Nanog axis is a therapeutic target for the treatment of PTX resistance in ovarian cancer management.
紫杉醇（PTX）是卵巢癌的标准一线治疗药物，但由于其具有多药耐药性，其疗效受到限制。因此，确定有效的药物靶点对于促进卵巢癌治疗对 PTX 的敏感性至关重要。本研究招募了 70 名接受 PTX 治疗的卵巢癌患者进行基因表达和生存率分析。在卵巢癌细胞（亲本和 PTX 耐药）和异种移植模型中进行了肌肉盲样蛋白 3（MBNL3）功能获得和功能丧失实验。检测并进行了癌细胞活力、细胞凋亡、球体形成、Nanog 基因沉默实验，以剖析 MBNL3 介导的 PTX 耐药的潜在机制。MBNL3 的高表达与卵巢癌的 PTX 耐药和预后不良呈正相关。MBNL3 通过上调 Nanog 增加卵巢干细胞样细胞的活力并减少细胞凋亡。本研究表明，MBNL3-Nanog 轴是治疗卵巢癌管理中 PTX 耐药的治疗靶点。
