L-门冬酰胺酶前体脂质体对小鼠毒性及对实验性肿瘤作用

Effect of L-Asparaginase, Proliposome on Toxicity in Mice and Experimental Tumor

目的 :研究 L-门冬酰胺酶 ( L-Asparaginase,L-A)前体脂质体 ( Proliposome,PL) [L-APL]iv对小鼠的毒性及对荷瘤小鼠的抗肿瘤活性。方法 :以小鼠的急性毒性和外周血中白细胞数及血小板数为指标观察药物对小鼠的毒性及以荷瘤小鼠的瘤重和生命延长率观察药物的抗肿瘤活性。结果 :L-APL i V对小鼠的急性毒性与 L -A相比明显降低 ,L-APL对正常小鼠外周血中白细胞数、血小板数无明显影响 ,而相同剂量 L-A对小鼠外周血中白细胞数、血小板数明显降低。与对照组相比 ,L-APL及 L-A ip可明显延长腹水型小鼠移瘤 L1 2 1 0 、P388的存活天数 ,与同剂量 L-A相比 ,L-APL高剂量有明显延长腹水型小鼠移植瘤的存活天数作用。L-APL及 L-A ip对小鼠移植瘤 Heps、EC实体型的肿瘤生长具有明显的抑制作用 ,两者抑瘤作用相近。结论 :L-APL对小鼠的毒性明显小于相同剂量的 L-A,L-APL不仅保持了 L-A的抗肿瘤活性 ,而且有明显的增效作用。

AIM: To study the toxicity of mice and the antitumor activity of L Asparaginase ( L A) proliposome(pl) [ L APL]. METHODS: Using acute toxicity and the peripheral leckocyte count and blood platelet count as index were observed the toxicities of L APL and L A, while the survival rate of mice with tumor was recorded to evaluate their antitumor activity. RESULTS: The acute toxicities of L APL was lower than L A by iv route . L APL had no effect on peripheral leukocyte count and blood platelet count of normal mice. On the contrary , L A had significantly effect on peripheral leukocyte count and blood platelet count with the same dose. Compared with the control, both L APL and L A could obviously prolong the survival days of mice with L 1210 , P 388 of ascitic type by ip route . Compared with L A , L APL with high dose could significantly prolong the survival days of mice of ascitic type. L APL and L A had good function of inhibition on the tumor growth of mice with Heps,EC. L APL and L A had almost the same function of inhibition of tumor. CONCLUSION: The toxicity of mice of L APL were much less serious than those of L A, L APL not only kept but also significantly strengthened the antitumor activity of L A.