The Antitumor Effect And Mechanism Of Lumbrokinase On Cancer

Objective To investigate the antitomor effects of lumbrokinase on cell proliferationand cell cycle of tumor cells and to explore its possible anti-tumor mechanisms.Methods MTT assay was used to determine the cell proliferation of different tumorcells (human hepatocarcinoma cell bel-7402; lung cancer cells A549and H1299) treatedby different concentrations of lumbrokinase for24h. Via a microscope, the changes in thetumor cell morphology were observed; Flow cytometry was performed to find thealterations of cell cycle. Furthermore, RT-PCR method was used to evaluate geneexpression of P53in the tumor cells. H22hepatoma ascites bearing mouse model was usedto observe the impact of lumbrokinase and earthworm extract on the quality of life andsurvival of ascites tumor mice.Results Lumbrokinase assumed a dose dependent manner in its inhibitory effect onhuman hepatocarcinoma cell bel-7402, lung cancer cells A549and H1299; and the halfinhibitory concentration (IC50) was25.45±1.88(U/ml),54.35±2.11(U/ml) and119.62±1.51(U/ml), respectively. After treated by lumbrokinase, the cell morphology changedsignificantly and the percent of floating cells increased with the increase in concentration oflumbrokinase; Flow cytometry results showed that lumbrokinase arrested the cell cycle inG1for7402and S phase for A549；RT-PCR analysis indicated that lumbrokinasesignificantly up-regulated the expression of p53in A549and7402. Animal experimentsshowed that lumbrokinase can significantly improve the life quality of ascites tumor miceand prolong their survival period.Conclusion Lumbrokinase can in vitro significantly inhibit tumor cell proliferation and in vivo can significantly improve the life quality and prolong the survival period of theascites tumor-bearing mice. Therefore, lumbrokinase can be used as anti-tumor drugcandidates.