The results indicated that IGF1R sequence-specific siRNAs induced profound IGF1R down-regulation without influencing IR expression and showed a clear correlation between the ability of siRNA and Perifosine figitumumab to inhibit the phosphorylation of specific down-stream signals, such as p-AKT and p-STAT3, only in sensitive cells. We also investigated the effects of IGF1R knockdown on the proliferation of sensitive cells and confirmed that silencing IGF1R expression resulted in an anti-proliferative effect on sensitive cells . In short, these results showed that the anti-proliferative effects of figitumumab are specifically mediated through the downregulation of AKT and STAT3 signaling pathways rather than through the ERK signaling pathway in sensitive cells which have a strong IGF1R signaling dependency. To further analyze the mechanisms through which figitumumab Temozolomide inhibited the proliferation and survival of cancer cells, we conducted a flow cytometric analysis . Figitumumab induced a similar dose-dependent increase in the percentage SNU719, HepG2, and SNU368 cell in the G1 Phase. However, there was no increased rate of apoptosis . This analysis showed that figitumumab decreased cell viability through cell cycle inhibition without inducing apoptosis. We next sought further evidence of figitumumab activity in vivo by using HepG2 to establish xenografts due to their sensitivity to figitumumab in vitro. To assess the effect of figitumumab on tumor growth in vivo, xenograft tumors were grown in athymic nude mice. As shown as shown in Figure 1D, repeated weekly administration of single dose of figitumumab to animals bearing HepG2 tumors resulted in substantial tumor growth inhibition for 21 d of figitumumab dosing and significantly inhibited tumor growth at day 17 . In addition, we tested the effect of figitumumab on IGF1R-related molecules after 1 d of figitumumab treatment. Figitumumab effectively reduced the levels of phosphorylated IGF1R and IRS1 . Taken together, these data showed that treatment with a single dose of figitumumab effectively inhibited the growth of tumors by inhibiting IGF1R and IRS1 activation. To identify a target for predicting sensitivity to figitumumab, expression of IGF1R related-proteins and downstream signaling molecules were analyzed in parallel by Western blotting. Interestingly, we found that figitumumab-sensitive cancer cells all overexpressed IGF1R; basal expression levels of IR were also much higher compared to that in other resistant cells . Based on a recent report , we expected that figitumumab would specifically inhibit the growth of cells overexpressing IGF1R or its phosphorylated form, but not ones overexpressing IR because figitumumab does not bind to IRs . However, IR protein levels were more responsive to figitumumab than any other protein.