ArticleOncotarget2016
The dual targeting of insulin and insulin-like growth factor 1 receptor enhances the mTOR inhibitor-mediated antitumor efficacy in hepatocellular carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
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- PER2 expression and cellular localization play a critical role in tumor aggressiveness and drug resistance in anCancer drug resistance (Alhambra, Calif.) · 2025Article
- 1,25‑Dihydroxyvitamin D3 mitigates the adipogenesis induced by bisphenol A in 3T3-L1 and hAMSC through miR-27-3p regulation.International journal of obesity (2005) · 2024Article
- Circulating myomiRNAs as biomarkers in patients with Cushing's syndrome.Journal of endocrinological investigation · 2024Article
- Vitamin D Reverts the Exosome-Mediated Transfer of Cancer Resistance to the mTOR Inhibitor Everolimus in Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- The Curious Case of the HepG2 Cell Line: 40 Years of Expertise.International journal of molecular sciences · 2021Review
- Dairy consumption and hepatocellular carcinoma risk.Annals of translational medicine · 2021Review
- Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?The journal of pathology. Clinical research · 2021Article
- Measurement and models accounting for cell death capture hidden variation in compound response.Cell death & disease · 2020Article
- Ataxia telangiectasia mutated pathway disruption affects hepatic DNA and tissue damage in nonalcoholic fatty liver disease.Experimental and molecular pathology · 2020Article
- Vitamin D reverts resistance to the mTOR inhibitor everolimus in hepatocellular carcinoma through the activation of a miR-375/oncogenes circuit.Scientific reports · 2019Article
- Article
- Multiscale systems pharmacological analysis of everolimus action in hepatocellular carcinoma.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Article
- Insulin-IGF signaling affects cell transformation in the BALB/c 3T3 cell model.Scientific reports · 2016Article
- Article
- Comparative transcriptomic analysis reveals the oncogenic fusion protein PAX3-FOXO1 globally alters mRNA and miRNA to enhance myoblast invasion.Oncogenesis · 2016Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulation of mTOR and IGF pathways is frequent in hepatocellular carcinoma (HCC), thus mTOR and IGF1R represent suitable therapeutic targets in HCC. The aim of this study was to evaluate the effects of mTOR inhibitors (mTORi) and OSI-906, blocker of IGF1R/IR, on HCC cell proliferation, viability, migration and invasion, and alpha-fetoprotein (α-FP) secretion. In HepG2 and HuH-7 we evaluated, the expression of mTOR and IGF pathway components; the effects of Sirolimus, Everolimus, Temsirolimus and OSI-906 on cell proliferation; the effects of Sirolimus, OSI-906, 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 HuH-7 present with the same mRNA expression profile with high levels of IGF2. OSI-906 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 Sirolimus-induced AKT activation as escape mechanism. Both agents demonstrated to be differently effective in inhibiting α-FP secretion. Sirolimus, OSI-906, and their combination, blocked cell migration and invasion in HuH-7. These findings indicate that, co-targeting of IGF1R/IR and mTOR pathways could be a novel therapeutic approach in the management of HCC, in order to maximize antitumoral effect and to prevent the early development of resistance mechanisms.
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