蛋白激酶抑制剂staurosporine增强抗癌药对肿瘤细胞的杀伤

蛋白激酶抑制剂staurosporine 5 ng·ml^-1阻断人胚肺2BS细胞于G₁/S边界,而不影响人胃癌BGC-823细胞的周期运行。细胞周期时相特异药物阿霉素、阿糖胞苷或博莱霉素A₅与staurosporine合用,2BS细胞和BGC-823细胞的IC₅₀均发生改变,显示低剂量staurosporine增强抗癌药对肿瘤细胞的杀伤。用谷胱甘肽(GSH)的荧光探针mBCL测定不同细胞周期时相的GSH,发现staurosporine使2BS细胞中GSH含量显著增高,而使BGC-823细胞中GSH含量显著下降。Staurosporine对正常和肿瘤细胞周期行进及胞内GSH水平的不同影响,可能是它增强抗癌药物对肿瘤细胞杀伤作用的原因。

PROTEIN KINASE INHIBITOR STAUROSPORINE ENHANCES CYTOTOXICITY OF ANTITUMOR DRUGS TO CANCER CELLS

Treated with low dosage(5 ng·ml^-1)of staurosporine for 18 h,human embryolung 2BS cells werc blocked at the G₁/S boundary, but human gastric carcinoma BGC-823 cells stillkept their cell cycle.In comparison with IC₅₀of 2BS and BGC-823 cells treated with cell cycle phasespecific antitumor drugs adriamycin,Ara-C and BLM A₅ alone or combined with staurosporine5ng · ml^-1),the IC₅₀values increased from 0.325 μg·ml^-1),5 μg · ml^-1)and 6.5 μg·ml^-1 )to 0.45 μg·ml^-1),10 μg · ml^-1)and 6.5 μg·ml^-1,respectively in 2BS cells;but decreased from 0.325 μg·ml^-1),25 μg·ml^-1)and 1.1 μg·ml^-1)to 0.07μg·ml^-1,6.25 μg · ml^-1)and 0.4 μg·ml^-1),respectively in BGC-823 cells.These results suggest that combination of staurosporine 5 ng·ml^-1)withantitumor drugs showed different effects on tumor cells and normal cells.With the GSH fluorescentprobe mBCL,we found that GSH contents incrcased in 2BS cells treated with staurcoporine 5ng·ml^-1).