The Synergic Inhibition of Wilforlide A With Cisplatin in Lung Cancer Is Mediated Through Caspase-3 and NFκB Signaling

Abstract

Lung cancer is a malignant disease in the respiratory system and accounts for hundreds of thousands of deaths each year. Cisplatin is the first-line drug in the clinic for lung cancer. However, drug resistance and side effects are becoming a big problem. Combination therapy is a good strategy to deal with this issue and has exhibited better efficacy. Wilforlide A (WA), a natural herb extract, has anti-inflammatory activity and increases the efficacy of docetaxel in prostate cancer. Accordingly, this study aims to investigate the role of WA in lung cancer. Here, WA was shown to inhibit proliferation and invasion in lung cancer but induced apoptosis. Combined administration of WA with cisplatin (WA/cisplatin) showed better efficacy to inhibit proliferation and to induce apoptosis. The level of total ROS was increased by WA, and WA/cisplatin treatment exhibited higher ROS production. Furthermore, WA was shown to induce the activity of the caspase-3-mediated signaling pathway, and this activation was enforced by WA/cisplatin. In addition, the critical members in NFκB signaling pathway, such as p65, IKK, and HDAC, were decreased by WA when IκB was increased reversely. In conclusion, this study suggests that WA is a promising molecule harboring the activity to inhibit the progression of lung cancer and to increase the efficacy of cisplatin.