Effects of Limonin on Immune Function and Apoptosis-related Factors Expression in MFC Gastric Cancer Bearing Model Mice / 中国药房

ABSTRACT

OBJECTIVE：To study the effects of limonin on immune function and apo ptosis-related factors expression in MFC gastric cancer bearing model mice. METHODS ：MFC gastric cancer bearing model was established by inoculating MFC gastric cancer cells into the right armpit of mice. After modeling ，model mice were divided into model group ，cyclophosphamide group （positive control ，25 mg/kg）and limonin high-dose ，medium-dose and low-dose groups （100，50 and 25 mg/kg），with 10 mice in each group. Other groups were given relevant medicine intragastrically ，once a day ，for consecutive 14 days，except that model group was given 0.5％ sodium carboxymethyl cellulose intragastrically. Before administration and after last administration ，the body weight of mice was measured ；spleen，thymus and tumor tissue were taken after the last administration to calculate the spleen index，thymus index and tumor inhibition rate. The percentage of CD 4+ and CD 8+ T lymphocytes ，CD4+/CD8+ ratio were detected by flow cytometry. The expression of immune function related indexes （IL-2，IL-10，IFN-γ）in serum were detected by ELISA. RT-PCR and Western blot assay were adopted to detect relative mRNA and protein expression of apoptosis-related factors [cytochrome C （Cyt-C），Bcl-2，Bax] in tumor tissue of mice. RESULTS ：There was no significant difference in body weight among the other groups except that of cyclophosphamide group was decreased significantly ，compared with model group （P＜0.05）. Inhibitory rate of tumor were （58.16 ± 7.07）％ ，（37.09 ± 4.26）％ ，（27.30 ± 3.64）％ ，（15.13 ± 2.95）％ in cyclophosphamide group ，limonin high-dose ，medium-dose and low-dose groups. Compared with model group ，spleen index ， thymus index ，the percentages of CD 4+ and CD 8+T lymphocyte cells ，CD4+/CD8+ ratio，serum levels of IL- 2 and IL- 10，relative mRNA and protein expression of Bcl- 2 in tumor of mice in cyclophosphamide group as well as the expression of IL- 10，relative mRNA and protein expression of Bcl- 2 in limonin groups were decreased significantly （P＜0.05）. The expression of IFN-γ，relative mRNA and protein expression of Cyt-C and Bax of cyclophosphamide group as well as spleen index （except for low-dose group ）， thymus index ， the percentage of CD 4 + and CD 8 + T lymphocytes，CD4+/CD8+ ratio，the expression of IL- 2 and IFN-γ，and relative mRNA and protein expression of Cyt-C and Bax in limonin groups were increased significantly （P＜0.05）. CONCLUSIONS ：Limonin can inhibit tumor growth in MFC gastric cancer bearing model mice ，and the side effects are relatively weak. Its mechanism is related to the improvement of immune function and the induction of apoptosis.