Curcumin Increased the Sensitivity of Non-Small-Cell Lung Cancer to Cisplatin through the Endoplasmic Reticulum Stress Pathway.

Abstract

Objective Non-small-cell lung cancer (NSCLC) is one of the most lethal cancers. Although cisplatin-based chemotherapies have been regarded as a promising treatment approach, cisplatin resistance still remains one of the major clinical challenges. Curcumin, a naturally occurring polyphenol, has been proved to increase chemotherapeutic efficiency of NSCLC cells. However, the role of curcumin in cisplatin-resistant NSCLC cells has been rarely investigated. This study aims to investigate whether curcumin enhances cisplatin sensitivity of human NSCLC cells and its underlying mechanisms. Method A549/DDP and H1299/DDP cells were treated by DDP or/and curcumin before cell viability, and apoptosis were determined by using a CCK-8 assay and flow cytometer. The expressions of apoptosis and ER stress-related proteins, including cleaved caspase-3, cleaved PARP, CHOP, GRP78, XBP-1, ATF6, and caspase-4, were measured by the qPCR and western blotting. After cotreatment by DDP and curcumin, A549/DDP and H1299/DDP cells were further treated by the ER stress inhibitor, salubrinal (20 μm), after which the cell apoptosis and viability were detected. Result Treatment by DDP and curcumin can substantially decrease cell viability, while can increase the cell apoptosis rate, elevate mRNA and protein expressions of apoptosis and ER stress-related proteins, compared with cells treated by DDP or curcumin alone. Salubrinal treatment can counteract the suppressive effect of DDP and curcumin on cell viability and decrease the cell apoptosis of A549/DDP and H1299/DDP cells. Conclusion Curcumin can increase the sensitivity of NSCLC to cisplatin through an ER stress pathway and thus can be served as one of the molecular targets for overcoming the cisplatin resistance.