胰岛素对人食管癌及肺腺癌化疗增效作用的研究

目的：探讨用胰岛素提高癌细胞生长代谢水平对化疗敏感性的影响。方法：选用人食管癌（NEC）及人肺腺癌细胞（GLC）为靶细胞,以胰岛素为细胞生长代谢促进剂,采用MTT比色分析法,分析细胞活力及细胞代谢,用流式细胞仪做细胞周期分析。结果：MTT比色分析法发现,胰岛素（2．0－15.0mU/ml)可增强足叶乙甙（30μg/ml)的细胞毒作用;细胞周期分析表明,胰岛素可增加顺铂、足叶乙甙、5－氟尿嘧啶对GLC的S期阻滞,增效幅度约80％;可增加5－氟尿嘧啶所致的G2M期阻滞,增效幅度约90％。细胞周期阻滞的最终结果是细胞死亡。同时发现胰岛素对NEC细胞的化疗增效作用较小。结论：初步证实“提高癌细胞的生长代谢水平,继之给予化疗,可提高化疗药物细胞毒作用”,为临床化疗增效提供了新的途径,具有理论及实践意义。

The effect of insulin on chemotherapeutic drug sensitivity in human esophageal and lung cancer cells

OBJECTIVE: To discuss the effect of insulin, as a metabolic promoter, on chemotherapeutic drug sensitivity in human esophageal and lung cancer cells. METHODS: Human esophageal cancer cells NEC and human lung adenocarcinoma cells GLC were cultured and then inoculated into the wells. MTT was added. Chemotherapeutic drugs, etopside, cisplatin, or 5-fluoto-uracilum was added to examine their cytotoxity activity. Then insulin of the final concentration of 5 mU/ml was added 8 hours before etopside (30 - 40 micro g/ml), cisplatin (2.5 micro g/ml), or 5-Fu (50 micro g/ml) was added. MTT A value was tested by colorimetry to evaluate the number of cancer cells, cell activity, and metabolism status so as to reflect the cytotoxity of the anti-tumor agent. Insulin was added into the suspension of cancer cells. Flow cytometry was used to detect the cell-cycle progresses. RESULTS: Insulin alone did not inhibit the cell growth and mildly promoted the cell metabolism with the concentration > 5 mU/ml. Insulin (2.0 - 15.0 mU/ml) enhanced the chemocytotoxity of etopside (30 micro g/ml) on human esophageal and lung cancer cells as indicated by MTT colorimetry. GLC cell cycle assay showed that the S phase block induced by etopside, cisplatin and 5-FU and the G(2)/M block induced by 5-FU were enhanced by insulin with the increased block rates of 80% and 90% respectively. The increased block rate induced by insulin in NEC cells was lower than in GLC cells. CONCLUSION: A reversible metabolic promoter, insulin enhances the cytotoxity of the chemotherapeutic agents. It is possible to increase the growth and metabolism of cancer cells first so as to enhance the chemosensibility, and then administer chemotherapeutic agents, thus improving their therapeutic effects.