Unraveling the Mechanism of Curculiginis Rhizoma in Suppressing Cisplatin Resistance in Non-Small Cell Lung Cancer: An Experimental Study

Xin Huang,1,* Meng Wang,1,* Baochen Zhu,1,* Yu Hao,2 Ruoyu Gao,2 Wenhui Liu,2 Jiaojiao Cheng,1 Guodong Hua,1 Chunmiao Xue1 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guodong Hua; Chunmiao Xue, Email zhaojhuagd@126.com; xuechunmiao9501@163.comIntroduction: Non-small cell lung cancer (NSCLC) stands as one of the most prevalent malignancies, and chemotherapy remains the primary treatment for advanced stages. However, the high expression of ABC binding cassette transporters, including MRP, P-gp, and LRP, along with multidrug resistance proteins, has been identified as a significant factor contributing to decreased chemotherapy drug sensitivity. This study aims to explore the impact and underlying mechanisms of Curculiginis Rhizoma [Hypoxidaceae; Curculigo orchioides Gaertn.] (CR) in combination with cisplatin on improving chemoresistance mediated by ABC binding cassette transporters and multidrug resistance proteins in NSCLC.Methods and Results: To unravel the relationship between JNK, MRP, P-gp, and LRP in NSCLC and gain insights into the regulatory mechanism of CR, this study employs an integrated approach encompassing bioinformatics, molecular docking, molecular dynamics, animal and cellular experiments. Bioinformatics analysis revealed a significant increase in the expression levels of JNK, MRP, P-gp, and LRP subtypes in multidrug-resistant non-small cell lung cancer. Subsequent animal experiments have shown that the combination of CR with cisplatin can improve the survival rate of lung cancer mice. Molecular docking and molecular dynamics analyses demonstrated favorable binding interactions between curculigoside and the aforementioned subtypes of JNK, MRP, P-gp, and LRP. In cellular experiments, the combi