蛋白激酶抑制剂staurosporine增强抗癌药对肿瘤细胞的杀伤

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

蛋白激酶抑制剂ｓｔａｕｒｏｓｐｏｒｉｎｅ５ｎｇ·ｍｌ￣（－１）阻断人胚肺２ＢＳ细胞于Ｇ＿１／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、阿糖胞苦或博莱霉素Ａ＿５与ｓｔａｕｒｏｓｐｏｒｉｎｅ合用，２ＢＳ细胞和ＢＧＣ－８２３细胞的ＩＣ＿（５０）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。

Treated with low dosage(5 ng·ml￣(-1)of staurosporine for 18 h,human embryolung 2BS cells werc blocked at the G_1/S boundary, but human gastric carcinoma BGC-823 cells stillkept their cell cycle.In comparison with IC_(50)of 2BS and BGC-823 cells treated with cell cycle phasespecific antitumor drugs adriamycin,Ara-C and BLM A_5 alone or combined with staurosporine5ng·ml￣(-1),the IC_(50)values increased from 0.325μg·ml￣(-1),5μg·ml￣(-1)and 6.5 μg·ml￣(-1)to 0.45μg·ml￣(-1),10μg·ml￣(-1)and 6.5μg·ml(-1),respectively in 2BS cells;but decreased from 0.325μg·ml￣(-1),25μg·ml￣(-1)and 1.1μg·ml￣(-1)to 0.07μg·ml(-1),6.25μg·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).