Home Blog of Signal Transduction PI3K/Akt/mTOR Akt Perifosine and ABT-737 synergistically inhibit lung cancer cells in vitro and in vivo

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Perifosine and ABT-737 synergistically inhibit lung cancer cells in vitro and in vivo

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.

Related Products

Cat.No. Product Name Information
S1037 Perifosine Perifosine is a novel Akt inhibitor with IC50 of 4.7 μM in MM.1S cells, targets pleckstrin homology domain of Akt. Phase 3.

Related Targets

Akt