Effect Of Sorafenib On Lymphangiogenesis And Lymph Node Metastasis Of Subcutaneous Transplanted Tumor Of Human Cholangiocarcinoma In Nude Mice

Objective: To study the effect of sorafenib on Lymphangiogenesis and lymph node metastasis of transplanted tumor of human cholangiocarcinoma in nude mice.Methods: Transplanted tumor of human cholangiocarcinoma in nude mice was estabished by subcutaneous vaccination of Cholangiocarcinoma cell lines QBC 939 .We randomly divided the mice into control group, sorafenib 30mg/kg.day group and 60mg/kg.day group after tumorigenicity, and then treated the groups with gavage method for 6 weeks. The growth of dose groups and control groups was observed with caliper. Using Immunohistochemistry method, lymphatic microvessles of the edge of the tumor was marked by LYVE-1. The differences of LMVD and VEGFR-3 mRNA expression was evaluated by using RT-PCR in different groups. HE staining the tumor's ipsilateral axillary lymph node , the occurrence rate of different groups of lymph node metastasis of Cholangiocarcinoma was investigated. Results:1. sorafenib significantly depress the growth of cholangiocarcinoma.2. Dose groups'LMVD was significantly less than control group with P<0.05.3. After 6 weeks'treatment of sorafenib, the expression of VEGFR-3 mRNA in dose groups was less than that in control group with a statistical significance(P<0.05).4. No occurrence of lymph node metastasis was found in the transplanted cholangiocarcinoma model.Conclusion: Sorafenib could significantly inhibit the growth of xenograft Cholangiocarcinoma in nude mice. Sorafenib might reduce LMVD by down-regulating the expression of VEGF-C/D and VEGFR-3 signaling axis in Tumor edge.Conclusion:1.Sorafenib could significantly inhibit the growth of xenograft Cholangiocarcinoma in nude mice2.Sorafenib might reduce LMVD by down-regulating the expression of VEGF-C/D and VEGFR-3 signaling axis in Tumor edge.