【摘要】 背景与目的尼妥珠单抗是一种针对表皮生长因子受体的人源化Ig G1型单克隆抗体,可在多种肿瘤中提高化疗和放射治疗的敏感性;而非小细胞肺癌常用化疗药物有多种,尼妥珠单抗对这些药物敏感性的影响尚缺乏报道。本研究探讨尼妥珠单抗对顺铂、吉西他滨、紫杉醇、培美曲塞、长春瑞滨在非小细肺癌细胞中敏感性的影响及可能机制。方法选择PC9人肺癌细胞作为观察对象,WST-1法检测细胞增殖率、流式细胞仪检测细胞周期、TUNEL法检测细胞凋亡率、免疫荧光染色联合激光扫描共聚焦显微镜下观察细胞内微管、微丝的分布情况。结果尼妥珠单抗联合紫杉醇对PC9细胞的增殖抑制最为显著(P<0.05),细胞凋亡率显著增加(P=0.013),细胞发生G2/M期阻滞的比例显著提高(P<0.05);共聚焦显微镜下观察提示尼妥珠单抗促进PC9细胞中的微管和微丝聚集且排列整齐。结论尼妥珠单抗能够显著提高紫杉醇在PC9细胞中的敏感性,机制可能与促进微管、微丝聚集和诱导G2/M期阻滞有关。尼妥珠单抗联合紫杉类药物可能是治疗非小细胞肺癌的一个潜在有效方案。更多还原

【Abstract】 Background and objective Nimotuzumab is a humanized Ig G1 type monoclonal antibody targeting epidermal growth factor receptor, and can enhance chemosensitivity and radiosensitivity of certain cancers. The aim of this study is to investigate the effects of nimotuzumab on the chemosensitivities of PC9 human lung adenocarcinoma cells to common chemtherapeutic drugs including ciaplatin, gemcitabine, paclitaxel, pemetrexed and vinorelbine, and to elucidate possible mechanisms. Methods PC9 human lung adenocarcinoma cell line was used in the study. Cell proliferation was determined by WST-1 assay and cell apoptosis was detected by TUNEL assay. Cell cycle distribution was analyzed by DNA analysis with FACS. Tublin and microfilaments were observed by immunofluorescence staining. Results Nimotuzumab significantly enhanced the chemosensitivity of PC9 cells to paclitaxel. Cell proliferation was inhibited significantly(P<0.05) and cell apoptosis rate was higher in nimotuzumab combined with low dose paclitaxel(0.05 μg/m L) group(P=0.013). G2/M arrest was increased significantly by nimotuzumab combined with paclitaxel group(P<0.05). Nimotuzumab caused aggregation of tublin and microfilaments into well organized microtubules. Conclusion Nimotuzumab enhanced the chemosensitivity of PC9 cell to paclitaxel by enhancing G2/M arrest and aggregation of tublin and microfilaments. Therefore, Nimotuzumab combined with taxane drugs could be a potential effective regimen in non-small cell lung cancer.更多还原