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目的:探讨中华眼镜蛇毒(Naja Naja Actra Venom,NNAV)抗白血病作用。方法:应用不同剂量NNAV和阿霉素(THP)于人红白血病细胞株(K562)和难治性白血病细胞株,观察NNAV直接或协同THP的细胞毒性及采用流式细胞仪进行凋亡检测。结果:NNAV对K562有明显的细胞毒及促进细胞凋亡作用,并剂量依赖地增强THP杀伤作用。但对难治性白血病细胞株作用不一:单用NNAV有细胞毒性25%(5/20);单用无效联合THP有效55%(11/20),以NNAV 100μg/ml+THP 5μg/ml作用最强;凋亡百分率增多60%(12/20)。临床对比研究结果,体外实验THP及NNAV无效的9例病人,含蒽环类全部无效(其他机制药物有效3例);THP及NNAV有效的5名病人,含蒽环类缓解2例,1例其它药物缓解;双相吻合率超过60%。结论:NNAV体外对难治性白血病细胞株有一定杀伤作用,和适当剂量THP合用有效率及杀伤作用明显增加,提示蛇毒中可能含有特殊抗难治性白血病的组分。
Objective: To investigate the anti-leukemia effect of Naja Naja Actra Venom (NNAV). Methods: NNAV and doxorubicin (THP) were used in human erythroleukemia cell line (K562) and refractory leukemia cell lines to observe the cytotoxicity of NNAV directly or in combination with THP and apoptosis detection by flow cytometry. Results: NNAV had obvious cytotoxicity and apoptosis effect on K562 cells and increased the killing effect of THP dose-dependently. But had no effect on refractory leukemia cell lines: cytotoxicity was 25% (5/20) with NNAV alone and 55% (11/20) with no effective combination with THP, with NNAV 100μg / ml + THP 5μg / ml The strongest effect; the percentage of apoptosis increased by 60% (12/20). The results of clinical studies, in vitro experiments THP and NNAV invalid 9 patients, including anthracycline null and void (other mechanisms of drug effective in 3 cases); THP and NNAV effective 5 patients, including anthracycline relief in 2 cases, 1 case Other drugs to ease; two-phase anastomosis rate of more than 60%. CONCLUSION: NNAV can kill some refractory leukemia cells in vitro, and its efficiency and cytotoxicity are obviously increased with the appropriate dosage of THP, suggesting that the snake venoms may contain special anti-refractory leukemia components.