Endoplasmic reticulum stress (ERs) has been regarded as an important cause for the pathogenesis of non-small-cell lung cancer (NSCLC). β-elemene is an active component in the essential oil extracted from a medicinal herb， Curcuma wenyujin， and has been reported to be effective against non-small-cell lung cancer (NSCLC). However， the potential effect and underlying mechanisms of β-elemene on regulating ERs to inhibit NSCLC are still unclear. In the present study， A549 cells and Lewis tumor-bearing C57BL/6J mice were established to evaluate this effect. Visualsonics Vevo 2100 Small Animal Dedicated High-frequency Color Ultrasound was performed to observe tumor volume in vivo. 3-(4，5-dimethylthiazol-2-... More
Endoplasmic reticulum stress (ERs) has been regarded as an important cause for the pathogenesis of non-small-cell lung cancer (NSCLC). β-elemene is an active component in the essential oil extracted from a medicinal herb， Curcuma wenyujin， and has been reported to be effective against non-small-cell lung cancer (NSCLC). However， the potential effect and underlying mechanisms of β-elemene on regulating ERs to inhibit NSCLC are still unclear. In the present study， A549 cells and Lewis tumor-bearing C57BL/6J mice were established to evaluate this effect. Visualsonics Vevo 2100 Small Animal Dedicated High-frequency Color Ultrasound was performed to observe tumor volume in vivo. 3-(4，5-dimethylthiazol-2-yl)-2，5- diphenyltetrazolium bromide (MTT) was used to evaluate cell vitality of A549 cells. Furthermore， western blotting (WB)， immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (q-PCR) were applied to detect the ERs-related proteins. Flow cytometry was also applied to detect cell apoptosis and assay kit for reactive oxygen species (ROS) generation. Our results showed that β-elemene inhibited lung cancer tumor growth and cell vitality in a dose- and time-dependent manner. Not only that， β-elemene could up-regulate ERs-related proteins like PERK， IRE1α， ATF6， ATF4， CHOP and down-regulate the Bcl-2 expression. More importantly， ERs inhibitor 4-PBA， IRE1α inhibitor STF-083010， ATF6 inhibitor Anti-ATF6 and PERK inhibitor GSK2656157 can all reduce the amplitude of protein expression changes and apoptosis rates， then weaken the anti-tumor effect of β-elemene. Therefore， the present in vivo and in vitro study revealed that the anti-NSCLC effect of β-elemene is closely related to the activation of ERs through PERK/IRE1α/ATF6 pathway， and this might be beneficial for clinical therapy of NSCLC.
