HSPA12B overexpression induces cisplatin resistance in non-small-cell lung cancer by regulating the PI3K/Akt/NF-κB signaling pathway

摘要

Although cisplatin (CDDP) is widely used for non-small-cell lung cancer (NSCLC) treatment, resistance remains a major problem that restricts its efficacy. Therefore, identification of drugs that reverse or prevent resistance to CDDP in NSCLC has been a focus of a number of studies. The results of the present study revealed the effect of heat shock protein family A member 12B (HSPA12B) overexpression on chemoresistance in A549 cells in vitro. The effect of HSPA12B overexpression on chemoresistance in mice bearing A549 xenografted tumors was then determined via stable HSPA12B transfection. Finally, the effects of HSPA12B overexpression on the phosphorylation of protein kinase B (Akt) and nuclear factor-κB inhibitor α (IκBα), and the expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and the pro-apoptotic protein cleaved caspase-3 were determined by western blot analysis. The results demonstrated that HSPA12B overexpression increased resistance to CDDP in NSCLC cells in vivo and in vitro by promoting cell growth and inhibiting CDDP-induced apoptosis. Mechanistically, this effect was mediated by the upregulation of phosphorylated (p-)Akt, p-IκBα and Bcl-2 and the downregulation of cleaved caspase-3. Therefore, the present study provides useful information pertaining to the identification and targeting of a CDDP-resistant population, and the development of potential therapeutics to improve the current treatment modalities in NSCLC.