MP92-13 NOVEL COMBINATION TREATMENT (OGX427/ SORAFENIB) ENHANCES SENSITIVITY IN RENAL CELL CARCINOMA

be solved.We show that the autocrine secretion of IL-6 induced by TKIs-stimulation causes activation of AKT-mTOR pathway, and also show that combination therapy with IL-6 receptor antibody and TKI reduces angiogenesis and GLUT1 expression.METHODS: Human renal cell carcinoma cell line 786-O was used for this study.Sorafenib, sunitinib and pazopanib were used as TKIs.GLUT1 expreiion and VEGF secretions from 786-O cells cultured with TKIs were measured by real time PCR and ELISA.Western blot analyses were applied for detection of GLUT1 as well as activated Akt, mTOR proteins.The growth of tumors in athymic mice receiving combination therapy with tocilizumab and sorafenib were compared with those in the sorafenib treated mice.The effects of the combination therapy were evaluated by FDG-PET and immunohistochemical examinations for CD31 and GLUT1.RESULTS: The 786-O RCC cell line secreted IL-6 and VEGF when they were cultured with TKIs.Western blot analysis revealed that Akt and mTOR were phosphorylated by TKI treatment.Tocilizumab treatment in combination with TKIs reduced activation of IL-6 signaling pathway and also suppressed cell proliferation and GLUT1 expression.The mean SUV max was decreased on day 3 in athymic mice receiving combination therapy with tocilizumab and sorafenib in comparison with those in the sorafenib alone (9.8AE1.6 vs. 11.5AE0.8respectively.p-0.04).No histopathological differences were found on day 3 despite decreased CD31 positive cells.On the day 21, the CD31 positive cells increased again in the tumors of sorafenib monotherapy.In contrast, when tocilizumab was given with sorafenib the tumor showed extensive central necrosis with absence of CD31 positive cells.CONCLUSIONS: Our results indicate that TKI treatment induces GLUT1 expression on RCC cells.IL-6 antibody in combination with TIK would restrain angiogenesis and GLUT1 expression on RCC.