Objective: To study the synergistic inhibitory effects of basic fibroblast growth factor (bFGF) monoclonal antibody (bFGF mAb) and irinotecan on the proliferation of small cell lung cancer H223 cells.
Methods: CCK-8 assay and flow cytometry were used to assess the effects of bFGF mAb combined with irinotecan on the proliferation and apoptosis of H223 cells, respectively. Western blotting was performed to analyze the effect of bFGF-mAb combined with irinotecan on AKT and ERK1/2 phosphorylation in the cells.
Results: Both bFGF mAb and irinotecan alone inhibited H223 cell proliferation in a dose-dependent manner (P<0.05). The inhibitory rate was significantly higher in H223 cells treated with bFGF mAb + irinotecan (54.30%) than in cell treated with bFGF mAb (18.73%) or irinotecan (21.96%) alone (P<0.05). Both bFGF mAb and irinotecan induced H223 cell apoptosis in a dose-dependent manner (P<0.05), and the combined treatment resulted in a significantly higher early apoptosis rates (6.5%) than treatment with bFGF mAb (2.7%) or irinotecan (4.3%) alone (P<0.05). bFGF mAb and irinotecan, either alone or in combination, significantly inhibited the levels of p-AKT protein and p-ERK1/2 protein without obviously affecting AKT and ERK1/2 protein levels.
Conclusion: bFGF mAb and irinotecan produce synergistic inhibitory effects on small cell lung cancer H223 cells by suppressing proliferation and promoting apoptosis of the cells, and can effectively block the MAPK/ERK and PI3K/AKT signaling pathways associated with bFGF.
目的: 探讨碱性成纤维生长因子(bFGF)单克隆抗体与伊立替康联合应用体外对抑制小细胞肺癌细胞株增殖和凋亡的作用及可能机制。
方法: CCK8检测bFGF单克隆抗体联合伊立替康对小细胞肺癌株H223增殖的抑制作用。AnneginV-FITC/PI染色流式细胞仪检测新型bFGF单克隆抗体联合伊立替康对小细胞肺癌株H223凋亡的影响。Western blotting分析bFGFmAb联合CPT-11对AKT和ERK1/2磷酸化水平的影响。
结果: bFGF单克隆抗体、伊立替康剂量依赖性抑制小细胞肺癌株H223的增殖，bFGF单克隆抗体组、伊立替康组及bFGF单克隆抗体联合伊立替康组对小细胞肺癌株H223的增殖抑制率分别为18.73%、21.96%、54.30%，联合用药组抑制率明显高于单药组(P < 0.05)。bFGF单克隆抗体、伊立替康剂量依赖性诱导小细胞肺癌株H223的凋亡，bFGF单克隆抗体组、伊立替康组及bFGF单克隆抗体联合伊立替康组诱导小细胞肺癌株H223的早期凋亡率分别为2.7%、4.3%、6.5%，联合用药组凋亡率明显高于单药组(P < 0.05)。bFGF单克隆抗体组、CPT-11组及bFGF单克隆抗体联合CPT-11组可明显抑制p-AKT蛋白和p-ERK1/2蛋白的水平，差异有显著性，而对AKT、ERK1/2蛋白则影响不大。bFGF抗体联合CPT-11一方面通过抑制p-AKT蛋白和p-ERK1/2蛋白的水平来抑制肿瘤细胞的增殖和转移。
结论: bFGF单克隆抗体联合伊立替康对小细胞肺癌株H223具有协同抑制作用，其机制与抑制细胞增殖和促进细胞凋亡有关。信号通路分析结果表明bFGF单克隆抗体联合伊立替康能有效阻断与bFGF相关的MAPK/ERK和PI3K/AKT信号通路。