The Inhibitory Effect Of Artemether And Cisplatin In Lewise Lung Cancer Bearing C57BL/6J Mice

Objective:To establiish a modelof the Lewise Lung Cancer Bearing C57BL/6J Mice.And base on the model, purpose to explore the the inhibitory effect and its mechanism.To study the best combination of delivery methods and the changes in immune function of mice.Method:1. Lewis lung carcinomal cells in vitro.2. To establiish a modelof the Lewise Lung Cancer Bearing C57BL/6J Mice. C57BL/6J mice subcutaneous planted with 3LL lung cancer cell (4×105) were randomly divided into 6 groups, A group of 10,when the tumor began to grow to about 6 mm in diameter.①. NS group;②. Artemether alone group;③. Cisplatin alone group;④. Artemether first and then use the cisplatin group;⑤. Cisplatin first and then use the artemether group;⑥. The same time give artemether and cisplatin group. Each group were administration by intraperitoneal injections. Fourteenth day after starting treatment, dissected tumor tissue in each group.3. Observing the survival status of mice in each group, weight changes, changes in tumor volume, tumor inhibition rate, changes in immune function, the pathological changes of tumor tissue by HE staining,apoptosis of tumor cells,and to detect the tumor cells cycle and the expression of related apoptosis gene Fas, FasL, P53, Bcl-2 by FCM. Evaluation the antitumor effect in many different orders of combined treatment groups.To study the anti-tumor effect and the mechanism of artemether and cisplatin in lung cancer bearing C57BL/6J mice. Results:1. Artemether alone and with cisplatin could improve the quality of life in tumor-bearing mice.2. Compared with the saline group, the body weight of mice increase slowly significant in mice in combination therapy(P<0.05), but also significantly slower than the artemether alone and cisplatin alone group(P<0.05); Changes in body weight of mice did not differ between the combined treatment groups(P>0.05); Compared with artemether monotherapy group, Body weight of mice does not increase significantly in cisplatin monotherapy group(P>0.05).3. Increase in tumor volume, the combined treatment group were significantly slower than the NS(P<0.05), but also growth slower than use the drug artemether or cisplatin alone group(P<0.05). Compared with NS group,the tumor volume growth rate of artemether group or cisplatin group is slower(P<0.05).4. The tumor inhibition rate of artemether group and cisplatin group were 36.44% and 50.29%, The tumor inhibition rate of combined treatment (first give artemether group, first give cisplatin group, the same time give artemether and cisplatin group) were (62.15%,65.54%,66.67%) compared with artemether alone group or cisplatin alone group(P<0.05).There was no difference for the tumor inhibition between the combined treatmentthe groups (P> 0.05), not related to the order of administration.5. Kim's formula is used to evaluate the synergy of combined treatment:the q values for the three modes of combined treatment are 0.85≤q≤1.15, that showed the additive inhibition of combined artemether and cisplatin in mice Lewis lung cancer.6. Compared with other treatment groups, a large of necrotic tumor tissue is scattered in each combined treatment group. This shows that the combination of artemether and cisplatin inhibited the growth of Lewis lung tumors in mice.7. The T lymphocyte sub-type results for a single use of artemether group and the combined group after treatment closer to the normal state before inoculation.This indicates that the artemether for the regulation of immune function is beneficial.It can enhance immune function of mice with Lewis lung cancer.8. Combined artemether and cisplatin can enhance the tumor cells apoptosis and promot its necrosis in mice. Compared with the saline group, artemether monotherapy group and monotherapy cisplatin group the apoptosis rate and necrosis rate is significantly different in combined treatment groups (P<0.05) However, no difference between the combination groups (P> 0.05);Artemether or cisplatin alone group compared with the saline group were significantly different (P<0.05); However, no difference between the artemether monotherapy group and monotherapy cisplatin group(P> 0.05).9. Compared with other treatment groups,combined artemether and cisplatin can arrest the tumor cells in in G0/G1 phase.10. Compared with the saline group, artemether monotherapy group and monotherapy cisplatin group the expression of apoptosis associated gene FasL/Fas and P53 were up regulated, the Bcl-2 was down regulated in the combination groups.Conclusion:Combined artemether and cisplatin can improve the quality of life in mice. The combination therapy groups were provided with anti-tumor effect to lung cancer bearing C57BL/6J mice at certain range of dosage. Artemether also can enhance immune function of mice with Lewis lung cancer. Combined artemether and cisplatin can promote a large necrotic of tumor tissue. It can induce apoptosis of lung cancer cell. Its mechanism might relate to cell cycle arrest and modulation of the apoptosis associated gene expression.