^(131)I-GMBP1对胃癌多药耐药细胞的细胞毒和诱导凋亡作用

Effect of radiolabeled GMBP1 peptide on cytotoxicity and induction of apoptosis of multiple drugs resistance cells in gastric cancer

目的:探讨131I-GMBP1对胃癌多药耐药细胞的细胞毒和诱导凋亡作用。方法:应用Iodogen方法将GMBP1与131I进行放射性标记,并检测其稳定性。应用MTT试验检测131I-GMBP1对胃癌多药耐药细胞SGC7901/ADR的细胞毒作用。流式细胞仪及Hoechst染色试剂盒检测131I-GMBP1诱导的胃癌多药耐药细胞SGC7901/ADR的凋亡作用。结果:131I-GMBP1的放射性标记率为9 3%-9 8%,放射性比活度为906.5GBq/mmol。131I-GMBP1对胃癌多药耐药细胞SGC7901/ADR具有明显的细胞毒作用,能够显著抑制其增殖。在SGC7901/ADR与131I-GMBP1共孵育96h后,其IC50值为0.83μg/ml。SGC7901/ADR与不同浓度GMBP1、131I及131I-GMBP1共孵育60h后,131I-GMBP1处理过的SGC7901/ADR细胞出现明显的细胞凋亡,呈药物浓度依赖性。131I-GMBP1最高浓度时细胞凋亡率约34.1%。131I-GMBP1对胃癌多药耐药细胞的细胞毒及凋亡作用与131I-GMBP1的浓度及耐药细胞共孵育时间有关。结论:131I-GMBP1对胃癌多药耐药细胞具有很强的细胞毒及凋亡作用,可为进一步探讨131I-GMBP1单独或联合传统的抗肿瘤药物治疗胃癌多药耐药临床应用的可行性提供了实验依据。

Objective：To explore the effect of 131I-GMBP1 on cytotoxicity and induction of apoptosis of multiple drugs resistance（MDR） cells in gastric cancer.Methods： The Iodogen tube method was used to label GMBP1 with 131I.The cytotoxicity of 131I-GMBP1 on gastric cancer MDR cell SGC-7901/ACR was determined by MTT assay.Apoptosis of gastric cancer MDR cell SGC7901/ADR induced by 131I-GMBP1 was investigated by flow cytometry and Hoechst Staining Kit.Results： The radiolabeling efficiency and specific activity of 131I-GMBP1 was 93%-98% and 906.5GBq/mmol,respectively.131I-GMBP1 had remarkable cytotoxic effects on SGC-7901/ACR and could significantly inhibit the growth of SGC-7901/ACR.The IC50 of SGC-7901/ACR was 0.83μg/ml after 96 h exposure to 131I-GMBP1.After 60 h exposure to different concentration of 131I-GMBP1,131I and GMBP1,SGC-7901/ADR treated with 131I-GMBP1 showed pronounced cell apoptosis in a concentration-dependent manner.The highest cell apoptosis rate was 34.1%.The effect of 131I-GMBP1 on the cytotoxicity and induction of apoptosis of gastric cancer MDR cells was dependent on the concentration and time of 131I-GMBP1 exposure.Conclusion： 131I-GMBP1 has strong effects on cytotoxicity and induction of apoptosis of gastric cancer MDR cells.These results provide an experimental basis for possible clinical application of 131I-GMBP1 alone or in combination with conventional antineoplastic agents in the treatment of MDR tumors.