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Ref Type Journal Article
PMID (27073162)
Authors Shen J, Xu L, Zhao Q
Title Perifosine and ABT-737 synergistically inhibit lung cancer cells in vitro and in vivo.
Journal Vol Issue Date Pages Journal Short Title
Biochemical and biophysical research communications 473 4 2016 May 13 1170-1176 Biochem Biophys Res Commun
URL
Abstract Text Here we explored the potential synergism between the novel Bcl-2 antagonist ABT-737 and the AKT inhibitor perifosine in lung cancer cells. Our in vitro results showed that perifosine and ABT-737 synergistically induced growth inhibition and apoptosis in both established (A549 and H460 lines) and patient-derived lung cancer cells. The combined activity was dramatically more potent than either single agent. For the molecular study, we showed that perifosine downregulated Mcl-1 expression, thus potentiating ABT-737 lethality against lung cancer cells. Exogenous over-expression of Mcl-1 remarkably attenuated perifosine plus ABT-737 combo-induced lung cancer cell apoptosis. In vivo, perifosine and ABT-737 co-administration strikingly inhibited A549 lung cancer xenograft growth in nude mice. The combined treatment in vivo was again superior than single treatment establishing a synergistic activity. Mcl-1 expression was also downregulated in combo-treated A549 tumors. The results of this preclinical study support the feasibility of further investigation of the perifosine plus ABT-737 regimen in future lung cancer clinical tests.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References