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目的初步了解钙调蛋白抑制剂及与化疗药物联用时对肝癌细胞增殖的影响,方法用钙调蛋白抑制剂W-7[N-(6-氨基己烷基)-5-氯-1萘-磺胺]处理肝癌细胞(Alexander株),观察不同浓度W-7对肝癌细胞摄取[3H]-TdR的影响、对ADMIC50的影响、与化疗药物(ADM,5-FU,MMC,VCR)联用时对肝癌细胞(Alexander株,离体肝癌细胞)杀伤的影响。结果①W-7能显著抑制肝癌细胞增殖,抑制效应与W-7的剂量及作用时间相关。②W-7能显著降低ADM对Alexander细胞的IC50。W-77.5μmol·L-1时,ADM的IC50为0.5mg·L-1;W-715μmol·L-1时,ADM的IC500.3mg·L-1,而对照为3mg·L-1。③与化疗药联用时,能提高化疗药物对肝癌细胞株及离体肝癌细胞的杀伤,并且其杀伤效果与W-7的浓度相关。结论钙调蛋白抑制剂对肝癌细胞的增殖有较强的抑制作用,可作为在肝癌患者化疗时一种辅助用药,增强化疗药物疗效、减少化疗药物用量,从而降低其毒副作用。
Objective To investigate the effect of calmodulin inhibitor and its combination with chemotherapeutic drugs on the proliferation of hepatocellular carcinoma cells. Methods Calmodulin inhibitor W-7 [N-(6-aminohexyl)-5-chloro-1 naphthalene- Sulfa] treatment of liver cancer cells (Alexander strain), observed the effect of different concentrations of W-7 on the uptake of [3H]-TdR by hepatoma cells, the effect on ADMIC50, and the combination of chemotherapy drugs (ADM, 5-FU, MMC, VCR) Effects of killing of hepatoma cells (Alexander strain, in vitro liver cancer cells). Results 1 W-7 could significantly inhibit the proliferation of hepatocellular carcinoma cells. The inhibitory effect was related to the dose and action time of W-7. 2W-7 can significantly reduce the IC50 of ADM on Alexander cells. At W-77.5 μmol·L-1, the IC50 of ADM was 0.5 mg·L-1; when W-715 μmol·L-1, the IC50 of ADM was 0.3 mg·L-1, while the control was 3 mg·L-1. 3 When combined with chemotherapeutic drugs, it can enhance the killing of chemotherapeutic drugs on liver cancer cell lines and isolated liver cancer cells, and its killing effect is related to the concentration of W-7. Conclusion Calmodulin inhibitor has a strong inhibitory effect on the proliferation of hepatocellular carcinoma cells. It can be used as an adjuvant drug in the treatment of liver cancer patients, enhance the efficacy of chemotherapy drugs, reduce the dosage of chemotherapy drugs, thereby reducing the toxic side effects.