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作 者:张迁[1] 秦一中[1] 万谟彬[1] 陈姬秀[1]
机构地区:[1]第二军医大学长海医院感染料,上海200433
出 处:《中国药理学通报》1998年第5期463-466,共4页Chinese Pharmacological Bulletin
摘 要: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。AIM To study the effects of calmodulin-antagonists associated with chemotherapy drug on hepatocarcinoma cells. METHODS One of the calmodulin-antagonists, W-7, has been used to treat hepatocarcinoma cells. The effects of different concentration of W-7 on the [3H]-TdR intake of alexander cells, on the ADM IC50, and on the hepatocarcinoma cells under being combined with chemotherapy drugs (ADM, 5-Fu, MMC, VCR) have been inverstigated. RESULTS ① W-7 can inhibit alexander cell proliferation in vitro correlated with dose dependent manner time course; ② W-7 can reduce the IC50 of ADM on alexander cell: when W-7 is 7. 5 μmolL-1, the IC50 is 0. 5 mg· L-1 land when W-7 is 15 μmol· L-1 IC50 is 0. 3 mg· L-1 ; whereas the control is 3 mg·L-1. ③ Combined with chemotherapy drugs, W-7 can enhance the killing effect on hepatocarcinoma cells and the kill rate is correlated with the concentration of W-7 under the same concentration of chemotherapy drugs. CONCLUSIONS W-7 can inhibit the proliferation of hepatocarcinoma cells, which can play a adjuvant role in the hepatocarcinoma chemotherapy, and enhance the treatment effect of chemotherapy.
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