重组L—门冬酰胺酶与其野生型在体外和体内的抗肿瘤作用比较

目的:研究重组L-门冬酰胺酶对肿瘤细胞体外生长及实验性肿瘤的抑制作用.方法:体外培养肿瘤细胞(K562、L1210和P815),分别用倒置显微镜和透射电镜观察肿瘤细胞的形态学,MTT比色法观察细胞增殖率及抑制率,流式细胞仪分析DNA含量.同时根据移植性肿瘤研究方法小鼠接种L1210、P388、Heps及S_(180)瘤株,观察给药后小鼠存活天数和瘤重.结果:体外细胞培养实验证明,重组L-门冬酰胺酶对K562、L1210和P815细胞生长具有显著抑制作用(P<0.01).体内实验表明,重组L-门冬酰胺酶ip能显著延长移植肿瘤小鼠(L1210和P388)的存活天数(P<0.01),并对小鼠移植性肝癌实体瘤(Heps)生长有明显的抑制作用(P<0.01)。重组L-门冬酰胺酶iv对小鼠Heps和S_(180)肿瘤生长有明显的抑制作用(P<0.01).结论:重组L-门冬酰胺酶对肿瘤细胞体外生长及受试肿瘤有明显抑制作用.本结果对重组L-门冬酰胺酶的临床应用提供实验依据.

Comparison of antitumor effect of recombinant L-asparaginase with wild type one in vitro and in vivo

AIM: To investigate the antitumor effect of recombinant L-asparaginase on the growth of several tumors such as P388, L1210, hepatocellular carcinoma (Heps), K562, P815, and sarcoma 180 (S180). METHODS: Tumor cells (K562, L1210, and P815) were cultured in vitro and the morphology of those cells was observed with inverse microscope and transmission electron microscope. MTT assay was performed to measure the cell proliferation and inhibition rate. DNA content was assayed by flow cytometry. According to protocols of transplant tumor research, mice were transplanted with tumor cells L1210, P388, Heps, and S180. The survival rate and weight of tumor were observed after the treatment of test drugs. RESULTS: The antitumor effects of L-asparaginase were observed in vitro with tumor cells K562, L1210, and P815 (P<0.01). In vivo experiments showed that ip adminis-tration of L-asparaginase significantly increased the survival rate and life span of mice with P388 or L1210 tumor cells (P<0.01). Tumor growth induced with Heps was also significantly suppressed. Furthermore, significant suppression of tumor growth was observed in mice induced with Heps and S180 by iv administration of L-asparaginase. CONCLUSION: Recombinant L-asparaginase markedly inhibited tumors tested in this study and the results strongly suggest that recombinant L-asparaginase has great potential for clinical treatment of these tumors.