85 Characterization of a Potent XIAP and CIAP1 Dual Antagonist in Models of Melanoma and Leukemia

on autophagy. Knockdown of Beclin 1 by siRNA protected cells from sorafenib-induced autophagy. Moreover, we examined the effect of SC59, a sorafenib derivative that closely resembles sorafenib structurally but with no kinase activity, in HCC. Interestingly, SC-59 demonstrated more potent than sorafenib on cell viability. SC-59 down-regulated P-STAT3 and induced autophagy in all tested HCC cell lines. Furthermore, our in vivo data showed that both sorafenib and SC-59 inhibited tumor growth, downregulated P-STAT3, enhanced the activity of SHP-1 and induced autophagy in Huh-7 tumors, suggesting that sorafenib and SC-59 activates autophagy in HCC. In conclusion, sorafenib and SC-59 induces autophagy in HCC through SHP-1-STAT3-Mcl-1-Beclin 1 pathway. Supported by NTUH101P01, NSC99-2314-B-002-017-MY2, and NSC1012325-B-002-032.