Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, 275 E Hancock St, Detroit, MI 48201, United States.
Department of Obstetrics and Gynecology, Augusta University, 1120 15th Street, BA-7300, Augusta, GA 30912, United States.
Gynecol Oncol. 2018 Mar;148(3):567-575. doi: 10.1016/j.ygyno.2017.12.018. Epub 2018 Jan 10.
The objective of this study was to determine the expression, and effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells.
CD11b expression was determined in epithelial ovarian cancer (EOC) cell lines and tissues by immunofluorescence and flow cytometry. Cytotoxicity of the CD11b antibody and synergism with chemothearapeutic drugs were determined by the MTT Cell Proliferation Assay in human macrophages, normal ovarian epithelial cells, and in both sensitive and chemoresistant EOC cell lines. Cell migration was assessed with a scratch assay and in vivo effects of the CD11b antibody was assessed with a nude mouse ovarian cancer xenograft model. Data was analyzed with either t-tests or one-way ANOVA.
CD11b was unexpectedly expressed in several EOC lines and tissues, but not normal tissues. Targeting CD11b with its monoclonal antibody resulted in intriguing cytotoxic effects in sensitive and chemoresistant EOC lines, while surprisingly not affecting normal cells. More importantly, the cytotoxicity of the CD11b antibody when combined with chemotherapeutic drugs (cisplatin or docetaxel) was significantly synergistic, in both sensitive and chemoresistant EOC cells. The anti-tumorigenic effect of the CD11b antibody was confirmed in an ovarian cancer nude mouse xenograft model.
Here we identify CD11b as a novel target, which selectively induces cytotoxicity in ovarian cancer cells.
本研究旨在确定 CD11b 在卵巢癌细胞中的表达及其靶向作用。
采用免疫荧光和流式细胞术检测上皮性卵巢癌（EOC）细胞系和组织中 CD11b 的表达。采用 MTT 细胞增殖检测法检测 CD11b 抗体的细胞毒性及其与化疗药物的协同作用，在人巨噬细胞、正常卵巢上皮细胞和敏感及耐药 EOC 细胞系中进行。通过划痕试验评估细胞迁移，并用裸鼠卵巢癌异种移植模型评估 CD11b 抗体的体内作用。采用 t 检验或单因素方差分析对数据进行分析。
CD11b 在几种 EOC 系和组织中出乎意料地表达，但在正常组织中不表达。用其单克隆抗体靶向 CD11b 可导致敏感和耐药 EOC 系产生有趣的细胞毒性作用，而对正常细胞却没有影响。更重要的是，CD11b 抗体与化疗药物（顺铂或多西他赛）联合使用时，在敏感和耐药 EOC 细胞中均具有显著的协同作用。CD11b 抗体在卵巢癌裸鼠异种移植模型中的抗肿瘤作用得到了证实。
本研究首次鉴定出 CD11b 是一种新的靶标，可选择性诱导卵巢癌细胞的细胞毒性。
