2Neurosurgery, Affiliated Hospital of Inner Mongolia Medical University, Huhehaote, 010051, China; fax: +86 (0471) 663-7640; E-mail: firstname.lastname@example.org
# These authors equally contributed to this work.
* To whom correspondence should be addressed.
Received May 4, 2013; Revision received September 13, 2013
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. Leptin is a pleiotropic hormone with antiapoptotic and proliferative roles involved in several systems. However, there is no known antiapoptotic mechanism of leptin in non-small cell lung cancer (NSCLC). So, we investigated the antiapoptotic mechanism of leptin in NSCLC. Proliferation, apoptosis, and the specific mechanism of leptin-transfected cells were analyzed in this study. Leptin, p-Perk, IRE1, cleaved ATF6, spliced XBP1, eIF2-α, TRAF2, CHOP, and caspase 12 proteins were detected by Western blot, and endoplasmic reticulum (ER) stress-related mRNA was detected by semi-quantitative reverse transcription PCR (RT-PCR). Leptin in A549 and transfected cells inhibited cisplatin-activated ER stress-associated mRNA transcription and activation of proteins. ER stress unfolded protein response (UPR) proteins, PERK and ATF6, were involved in leptin-triggered apoptosis. XBP1 and TRAF2 were increased significantly when treated with cisplatin in A549-siLPT and non-transfected cells. CHOP expression was blocked in A549 and transfected cells (LPT-PeP and LPT-EX cells). In conclusion, leptin can promote the proliferation of A549 cells through blocking ER stress-mediated apoptosis. This blocking is mediated by the p-Perk and ATF6 pathway through blocking activation of CHOP.
KEY WORDS: apoptosis, ER stress, cell growth, leptin, TRAF2, XPB1