中国实用妇科与产科杂志2026，Vol.42Issue(5)：560-564,5.DOI:10.19538/j.fk2026050115
GDF15单抗筛选及其联合卡铂逆转卵巢癌铂耐药的研究
Screening of anti-GDF15 monoclonal antibodies and their combination with carboplatin to reverse platinum resistance in ovarian cancer
摘要
Abstract
Objective To investigate the role of Growth Differentiation Factor 15(GDF15)monoclonal antibodies in reversing platinum resistance in ovarian cancer,to identify the most effective candidate antibody,and to explore the underlying molecular mechanisms.Methods This study was carried out from April 2025 to January 2026 at the Institute of Chemistry,Chinese Academy of Sciences,and the Cancer Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College.A platinum-resistant ovarian cancer cell line(SK-OV-3-R)and a patient-derived xenograft(PDX)model were established.Five GDF15 monoclonal antibodies were screened in parallel in vitro and in vivo to determine the optimal candidate.Cell viability was assessed by MTT assay,and apoptosis was evaluated using Annexin V-FITC/PI staining followed by flow cytometry.DNA damage was measured by γ-H2AX flow cytometry.AKT activator and inhibitor were applied to investigate the involvement of the PI3K/AKT signaling pathway.Tumor volume and tumor growth inhibition(TGI)were assessed in the PDX model.Results CTL-002 was identified as the most effective GDF15 monoclonal antibody.In SK-OV-3-R cells,CTL-002 combined with carboplatin significantly enhanced antitumor activity,reducing the IC50 from 29.47 μmol/L to 13.60 μmol/L and increasing the apoptosis rate to(26.85±1.6)％.Meanwhile,the combination treatment markedly increased γ-H2AX mean fluorescence intensity,indicating elevated DNA damage.Mechanistically,AKT inhibition mimicked the sensitizing effect of CTL-002,whereas AKT activatior partially reversed it.In the PDX model,the combination therapy significantly suppressed tumor growth,with a final tumor volume of(170.37±17.72)mm3 and a TGI of 66.3％,which was superior to carboplatin monotherapy(47.9％).Conclusion The anti-GDF15 monoclonal antibody CTL-002 can significantly enhance the in vitro inhibitory effect of carboplatin against platinum-resistant ovarian cancer and improve its antitumor efficacy in vivo,suggesting that anti-GDF15 monoclonal antibodies have potential clinical value for reversing platinum resistance in ovarian cancer.关键词
卵巢癌/GDF15/单克隆抗体/卡铂Key words
ovarian cancer/GDF15/monoclonal antibody/carboplatin分类
医药卫生引用本文复制引用
李泓瑶,孙怡,徐梦珂,赵丹..GDF15单抗筛选及其联合卡铂逆转卵巢癌铂耐药的研究[J].中国实用妇科与产科杂志,2026,42(5):560-564,5.基金项目
北京市自然科学基金(7252116) Beijing Natural Science Foundation(7252116) （7252116）
