It has been reported that chemotherapy resistance mainly contributed to treatment failure and poor survival in patients with ovarian cancer. Therefore, clarifying the molecular mechanism and identifying effective strategies to overcome drug resistance may play an important clinical impact on this malignant tumor. In our study, we found that the expression of Glycosyltransferase 8 domain containing 2 (GLT8D2) was significantly upregulated in ovarian cancer samples with CDDP (Cis-dichlorodiammine-platinum) resistance. Biological experiment demonstrate that GLT8D2 overexpression confers CDDP resistance on ovarian cancer cells; however, inhibition of GLT8D2 sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. By using affinity purification/mass spectrometry (IP/MS) and reciprocal co-immunoprecipitation (co-IP) analyses, we found that GLT8D2 interacts with fibroblast growth factor receptor 1(FGFR1) in ovarian cancer cells. Furthermore, overexpression of GLT8D2 activated FGFR/PI3K signaling axis and upregulated the phosphorylation levels of FRS2a and AKT (AKT serine/threonine kinase). Importantly, pharmacological inhibition of FGFR and PI3K (phosphatidylinositol 3-kinase) signaling pathway significantly counteracted GLT8D2-induced chemoresistance and enhanced platinum’s therapeutic efficacy in ovarian cancer. Therefore, our findings suggest that GLT8D2 is a potential therapeutic target for the treatment of ovarian cancer; targeting GLT8D2/FGFR/PI3K/AKT signaling axis may represent a promising strategy to enhance platinum response in patients with chemoresistant ovarian cancer.

据报道，化疗耐药主要是导致卵巢癌患者治疗失败和生存率低的主要原因。因此，阐明分子机制并确定克服耐药性的有效策略可能对这种恶性肿瘤具有重要的临床影响。在我们的研究中，我们发现含有 2 的糖基转移酶 8 结构域（GLT8D2）的表达在具有 CDDP（顺式二氯二胺铂）抗性的卵巢癌样本中显着上调。生物学实验证明GLT8D2过表达赋予卵巢癌细胞CDDP抗性；然而，在体外和体内，GLT8D2 的抑制使卵巢癌细胞系对 CDDP 细胞毒性敏感。通过使用亲和纯化/质谱 (IP/MS) 和相互免疫共沉淀 (co-IP) 分析，我们发现 GLT8D2 与卵巢癌细胞中的成纤维细胞生长因子受体 1（FGFR1）相互作用。此外，GLT8D2 的过表达激活 FGFR/PI3K 信号轴并上调 FRS2a 和 AKT（AKT 丝氨酸/苏氨酸激酶）的磷酸化水平。重要的是，对 FGFR 和 PI3K（磷脂酰肌醇 3-激酶）信号通路的药理学抑制显着抵消了 GLT8D2 诱导的化学耐药性，并增强了铂在卵巢癌中的治疗效果。因此，我们的研究结果表明 GLT8D2 是治疗卵巢癌的潜在治疗靶点；靶向 GLT8D2/FGFR/PI3K/AKT 信号轴可能代表一种有前景的策略，可增强化疗耐药卵巢癌患者的铂类反应。