The Study Of Antitumor Effects And Mechanism Of Artemisinin And Its Derivatives

1ObjectiveThe antitumor activites of artemisinin and its derivatives may become a hot research, it is hope to be developed into a new plant anticancer drug. This research study in vitro experiments to observe the antitumor effect of arte-misinin and its derivatives; By the way of animal experiments, in order to provide a reference for the further determine on the mechanism of its anti-tumor. Its next step in research scientific basis for the new use of old drugs to open a research idea.2Methods2.1Microculture tetrazolium assay was applied to test the cytotoxicity of artemisinin, dihydroartemisinine and artesunate to human lung cancer A549cell line and human sarcoma Hela cell line in vitro.2.2Modes was S180bearing mice by subcutaneous injection at the mouse axilla. KM mice under SPF was selected and randomly divided into eight groups, they were5-fluorouracil group (5-Fu), different doses of ART and DHA groups (200mg/kg,100mg/kg,25mg/kg/and model control group (Model), each group had10mice,24h later, each group was given drugs for14days. The general situation was observed and survival time in mice was compared, and measured cum survival of mice.2.3Modes was S180bearing mice by subcutaneous xenografts. KM mice under SPF was selected and randomly divided into eight groups, they were5-fluo rouracil group (5-Fu), different doses of ART and DHA groups (200mg/kg,100mg/kg,25mg/kg)and model control group (Model), each group had10mice,24h later, each group was given drugs for10days. The general situation was observed and survival time in mice was compare. Killed these mice in last given drug24h later. The tumor, spleen and thymus were weighted after complot dissection to calculate tumor inhibitory rate, spleen index and thymus index.2.4Establish mice model of lung cancer Lewis. The tumor bearing mice were randomly divided into control group, clophosphamide group (CTX), combined drugs group, high dosage of ART(200mg/kg), middle dosage of ART(100mg/kg), low dosage of ART(25mg/kg), each group contained6mice. After24h, inocul-ating tumor cells, These mice were given different drugs for12days, Tumor growth state was observed and tumor inhibitory rate was calculated24h later the last administration; enzyme-linked immunosorbent assay (ELISA) was used to detect IFN-γand TNF-a levels in tumor-bearing mice serum.3Results and Conclusion3.1Arteisinin, dihydroartemisinine and artesunate showed selective cytotoxicity to human lung cancer A549and human sarcoma Hela. Inhibition rate correlated with drug concentration, with the drug concentration turned low, the inhibition rate to A549and Hela cell lines turned down. The result of antitumor experiment in vitro suggests dihydroartemisinine and artesunate can significant antitumor effects of these tow cell lines, but arteisinin is nosignificant to A549cell line. Through MTT assay, results show ATS and DHA’s IC50is27.97μg/mL and43.9μg/mL to A549cell line, result show ATS, ART and DHA’s IG50is34.6μg/mL、48.1μg/mL and34.6μg/mL to Hela cell line.3.2Artemisinin and its derviatives can significantly inhibit S180tumor growth. The preliminary experimental result showed that:when the ART’s dosage is up to200mg/kg、100mg/kg and25mg/kg, percentage of antitumor is66.21、61.25and54.83; when the DHA’s dosage is up to200mg/kg、100mg/kg and25mg/kg, percentage of antitumor is55.53、54.55and48.36.The more the drug concentration, the higher the tumor inhibitory rate. In this reasech, ART and DHA have no harm on immune organs (spleen, shymus and so on) in S180cancer mice, the200mg/kg,100mg/kg and25mg/kg dose of ART and DHA can inhibit the growth of sarcom, and no significant toxicity on the immune system. The cum survival time of S180bearing mice showed:DHA200mg/kg. ART200mg/kg and100mg/kg doses can significantly prolong the survival time of tumor-bearing mice.3.3The result of antitumor experiment in vivo shows that ART can sign-ificant inhibit growth of Lewis tumor. When dosage is up to200mg/kg and100mg/kg, percentage of antitumor is36.06and23.84, respectively. Both of them have significantly effects as compared with control group (p<0.01), and that showed the additive inhibition of combined ART100mg/kg and CTX20mg/kg in mice Lewis lung cancer (percentage of antitumor is61.49, Gold-type formula obtained q=0.94). And we found that ART200mg/kg and100mg/kg can influe TNF-α and INF-γ level in tumor bearing mice serum(p<0.01), thus enhance tumor mice’s immune functions. This provided the experimental basis for the anticancer mechanism of the clinical use of artemisinin and its derivatives based drugs on the cytokine levels.