Inhibitory Effects Of Low-Molecular-Weight Citrus Pectin And Oxaliplatin On Colon Cancer Growth And Liver Metastasis In A Mouse Model

Background and objective:Galectin-3, aβ-galactoside-binding protein, has been involved in various physiological and pathological processes, such as cell growth, proliferation, differentiation, apoptosis, cell adhesion, angiogenesis, tumor progression and metastasis. The aim of this study was to investigate the effects of Low-Molecular-Weight Citrus Pectin (LCP),a galectin-3 inhibitor, combining with Oxaliplatin on the growth and liver metastasis of colon cancer in a nude model.Methods:1. The colon cancer and liver metastasis model was established using human colon cancer cell lines HT-29 by injecting into the subcapsule of the spleen in nude mice.2. Seven days after splenic injection,60 nude mice were randomized into four groups:①Control group,②LCP group,③O xaliplatin group, and④LCP+Oxaliplatin combination group, 15 nude mice every group(N=15). LCP was dissolved in distilled water and administered by daily oral gavage with a dose of 3g/kg. Mice in Control and Oxaliplatin group were given the same amount of distilled water instead;Oxaliplatin was solubilized in 5% glucose solution(GS) and injected intraperitoneally at a dose of 5mg/kg twice weekly. Mice in Control and LCP group were injected equivalent 5%GS instead of medication.3. All mice were sacrificed on day 28 after administration. The size of the spleen implanted tumor were measured, and the number of liver metastatic nodules were counted or the diameter of nodules were measured in each group mice. The spleen implanted tumor tissues and liver were resected and collected for further research.4. The expression of galectin-3 in spleen implanted tumor tissues was detected by immunohistochemistry.Results:1. The colon cancer and its liver metastasis nude model was established successfully.2. The percentage of spleen implanted tumor in Control, LCP, Oxaliplatin and Combination group was 93.3%, 93.3%, 92.9% and 93.3% respectively, and shown no significantly differences (all P>0.05). The size of spleen implanted tumor in LCP, Oxaliplatin and Combination group were significantly smaller than which in Control group ( P<0.05). The size of spleen implanted tumor in Combination group were markedly smaller than which in LCP and Oxaliplatin group (P <0.05).3. The percentage of liver metastasis in Control, Oxaliplatin, LCP and Combination group was 93.3%, 85.7%, 73.3% and 46.7% respectively. The number of liver metastatic nodules were significantly fewer or the diameter of nodules was markedly smaller in LCP and Combination group compared with which in Control group (P<0.05). Compared with LCP group, the number of liver metastatic nodules were significantly fewer or the diameter of nodules were markedly smaller in Combination group (P<0.05).4. The expression of Galectin-3 in spleen implanted tumor tissues in each group were shown no significantly differences (all P=0.859). Conclusion:1. LCP can inhibit the growth and liver metastasis of colon cancer.2. LCP combining with Oxaliplatin markedly inhibited the growth and liver metastasis of colon cancer, and those two agencies have synergistic effects.3. LCP did not inhibit the expression of galectin-3, and its inhibitory effects on the growth and liver metastasis of colon cancer may be achieved by binding to galectin-3 receptor and then inhibiting the function of galectin-3 or by other mechanism of action that has not been clarified.