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


CONCLUSIONS
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.
Guo
Qing-Long
QL
Department of Physiology, China Pharmaceutical University, Nanjing 210009, China. qinglongguo@hotmail.com
Wu
Min-Shu
MS
Chen
Zhen
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001215:Asparaginase / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D020014:K562 Cells / Q000473:pathology; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology*; D007941:Leukemia P388 / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012510:Sarcoma 180 / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D001215:Asparaginase