Enhancing Effect Of Xeloda On Sensitivity Of Lewis Lung Cancer To Radiation In Mice

Background Radiotherapy has become a primary methods of tumor therapy. But because of the existence of tumor hypoxic cell, it limits the efficacy of cancer radiotherapy further improvement. Now the domestic and the international are looking for increaseing tumor radiosensitivity drugs. Xeloda (capecitabine) is by far the only FDA and EMEA-approved oral fluorinated pyrimidine drugs. It is no cytotoxicity of its own and use high concentrations of intra-tumor thymidine phosphorylase (TP enzyme) into 5-Fu in the tumor selective activation of S-phase cells with a cell cycle specific cytotoxicity selectively block the cells at the G2/M phase to increase radiation sensitivity.Purpose Explore the role of Xeloda in enhancing the radiosensitivity.Materials and Methods First the tumor-bearing mouse model was induced by injecting Lewis lung cancer cells. To be 10-15 days after the tumor growth in mice to the lateral right lower limb≧0.5cm3,48 C57BL/6 mice were evenly randomized into 4 groups.Group A:the control group;Group B:the radiation group;Group C:the Xeloda group;Group D:the Xeloda plus radiation group.Group B and Group D were treated with Co60 Y radiation only(5Gy/F.on day 1,3,5 and 7;the total dose was 20 Gy);Group C and Group D use Xeloda 10-day,Xeloda dosage of 60mg/kg/d, dissolved in 200μl saline gavage to pour them into the mice stomach. At the same time Group A was fed with normal saline, normal saline dosage of 200μl/d, since the radiation therapy used in 10 days. During the experiment, observed changes in tumor size in each group.The tumor growth and tumor growth delays were observed in all groups. Meanwhile, the pathological change of the tumor tissue was observed with H-E staining method.And the apoplosis of tumor cells were examined with the method of TUNEL. The final statistics use SPSS 13.0 statistical software to apply processing.Results The Lewis lung cancer model was successfully established in mice.The tumor volumes of the treatment group were:Group A (5.85±1.77), Group B (4.73±1.87), Group C (4.81±1.89) and Group D (3.22±1.01).The tumor volume of Group D was the smallest (P<0.05).The tumor delays were 4.6 d in Group D,The sensitization enhancement ratio of Xeloda was 1.64.H-E staining showed that tumor necrosis in Group B,C and D was more severe than the control group,with the most severe one found in Group D.TUNEL results revealed that the apoptosis rate were(2.57±0.86)% in Group A, (4.76±1.10)% in Group B, (7.36±1.51)% in Group C, and (32.33±4.56)% in Group D;the apoptosis rate of every therapy group was higher than the control group, and the Group D significantly higher than the Group B and C (P＜0.01). Xeloda plus radiation group compared to other groups could significantly increase the tumor necrosis, promote cell apoptosis, reduce tumor size, delay in tumor growth.Conclusion Xeloda can dramatically increase the radiosensitivity of tumor cells and promotetheir apoptosis.