UNASSIGNED: Deregulation of @entity3470 and IGF pathways is frequent in @entity157 ( @entity157 ), thus @entity3470 and @entity2856 represent suitable therapeutic targets in @entity157 . The aim of this study was to evaluate the effects of @entity3470 inhibitors (mTORi) and @entity31057 , blocker of @entity2856 /IR, on @entity157 cell proliferation, viability, migration and invasion, and @entity160 (a-FP) secretion. In HepG2 and @entity5959 we evaluated, the expression of @entity3470 and IGF pathway components; the effects of @entity3446 , @entity2239 , @entity13850 and @entity31057 on cell proliferation; the effects of @entity3446 , @entity31057 , and their combination, on cell secretion, proliferation, viability, cell cycle, apoptosis, invasion and migration. Moreover, intracellular mechanisms underlying these cell functions were evaluated in both cell lines. Our results show that HepG2 and @entity5959 present with the same mRNA expression profile with high levels of @entity5100 . @entity31057 inhibited cell proliferation at high concentration, while mTORi suppressed cell proliferation in a dose-time dependent manner in both cell lines. The co-treatment showed an additive inhibitory effect on cell proliferation and viability. This effect was not related to induction of apoptosis, but to G0/G1 phase block. Moreover, the co-treatment prevented the @entity3446 -induced AKT activation as escape mechanism. Both agents demonstrated to be differently effective in inhibiting a-FP secretion. @entity3446 , @entity31057 , and their combination, blocked cell migration and invasion in @entity5959 . These findings indicate that, co-targeting of @entity2856 /IR and @entity3470 pathways could be a novel therapeutic approach in the management of @entity157 , in order to maximize antitumoral effect and to prevent the early development of resistance mechanisms.

The dual targeting of insulin and insulin-like growth factor 1 receptor enhances the @entity3470 inhibitor-mediated antitumor efficacy in XXXX .

@entity13850 :: ('MESH:C401859', 'Chemical') :: ['Temsirolimus'] @entity31057 :: ('MESH:C551528', 'Chemical') :: ['OSI-906'] @entity5100 :: ('3481', 'Gene') :: ['IGF2'] @entity5959 :: ('284424', 'Gene') :: ['HuH-7'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['Sirolimus'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity2239 :: ('MESH:C107135', 'Chemical') :: ['Everolimus'] @entity160 :: ('174', 'Gene') :: ['alpha-fetoprotein'] @entity157 :: ('MESH:D006528', 'Disease') :: ['HCC', 'hepatocellular carcinoma'] @entity2856 :: ('3480', 'Gene') :: ['IGF1R']
@entity157 :: (MESH:D006528,Disease) :: ['hepatocellular carcinoma']
