Peng Zhonglu, Xiao Xiang, Lu Xinyi, Cao Dong, Fang Huilong, Yang Zhiying, He Dongyang
School of Basic Medical Sciences, Xiangnan University, Chenzhou, China.
Sichuan University of Science & Engineering, Zigong, China.
IUBMB Life. 2025 Aug;77(8):e70043. doi: 10.1002/iub.70043.
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.
肺癌是呼吸系统的一种恶性疾病，每年导致数十万人死亡。顺铂是临床上治疗肺癌的一线药物。然而，耐药性和副作用正成为一个大问题。联合治疗是解决这一问题的良好策略，并且已显示出更好的疗效。雷公藤内酯醇A（WA）是一种天然草药提取物，具有抗炎活性，并能提高多西他赛在前列腺癌中的疗效。因此，本研究旨在探讨WA在肺癌中的作用。在此，WA被证明可抑制肺癌的增殖和侵袭，但可诱导细胞凋亡。WA与顺铂联合给药（WA/顺铂）显示出更好的抑制增殖和诱导凋亡的疗效。WA可提高总ROS水平，WA/顺铂治疗显示出更高的ROS产生。此外WA被证明可诱导半胱天冬酶-3介导的信号通路的活性，并且这种激活被WA/顺铂增强。另外，当IκB反向增加时，WA可降低NFκB信号通路中的关键成员，如p65、IKK和HDAC的水平。总之，本研究表明WA是一种有前景的分子，具有抑制肺癌进展和提高顺铂疗效的活性。
