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目的探讨表皮生长因子受体(EGFR)的单克隆抗体尼妥珠单(nimotuzumab,h-R3)与化疗药物联合对结肠癌细胞株LoVo的作用,初步探讨其可能的作用机制。方法采用MTT法测定不同药物单药、两药联合分别对结肠癌细胞株LoVo的IC50值;计算不同药物联合的q值,以确定药物联合的作用;流式细胞仪检测不同药物单药或者联合对细胞周期分布及凋亡比例的影响。结果联合h-R3能显著提高伊立替康对LoVo细胞的细胞抑制率,诱导更多肿瘤细胞发生凋亡以及产生G0/G1期、G2/M期阻滞,与5-氟尿嘧啶联合具有类似的作用,但较伊立替康不明显,而与奥沙利铂联合无明显增效作用。结论h-R3通过协同或相加作用提高伊立替康、氟尿嘧啶的细胞杀伤作用,其机制与促进细胞凋亡和影响细胞周期分布有关,奥沙利铂联合对LoVo细胞无明显增效作用。为进一步的体内及体外实验提供了一定的指导作用。
Objective To investigate the effect of combination of nimotuzumab (h-R3), a monoclonal antibody against epidermal growth factor receptor (EGFR), and chemotherapeutic drugs on colon cancer cell line LoVo and to explore its possible mechanism. Methods The IC50 value of different drug monotherapy and drug combination on colon cancer cell line LoVo was determined by MTT method. The q values of different drug combination were calculated to determine the effect of drug combination. Flow cytometry was used to detect single drug or combination of different drugs On the cell cycle distribution and apoptosis ratio. Results Combined with h-R3, the inhibitory rate of irinotecan on LoVo cells was significantly increased, more tumor cells were induced to apoptosis, and G0 / G1 phase and G2 / M phase arrest were found. Combined with 5-fluorouracil, h-R3 had a similar effect , But not obvious than irinotecan, but no significant synergistic effect with oxaliplatin. Conclusions h-R3 enhances the cytotoxicity of irinotecan and fluorouracil through synergistic or additive effects. The mechanism of h-R3 is related to the promotion of cell apoptosis and cell cycle distribution. Oxaliplatin combination has no synergistic effect on LoVo cells. For further in vivo and in vitro experiments provide some guidance.