Ophiopogonin B alleviates cisplatin resistance of lung cancer cells by inducing Caspase-1/GSDMD dependent pyroptosis

• Published in: Journal of Cancer Vol. 13; no. 2; pp. 715 - 727
• Main Authors: Cheng, Ziyu, Li, Zhihui, Gu, Ling, Li, Liqiu, Gao, Qian, Zhang, Xiongfei, Fu, Jin, Guo, Yuanyuan, Li, Qirui, Shen, Xu, Chen, Meijuan, Zhang, Xu
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 2022; Ivyspring International Publisher
• Subjects: Antibodies; Cancer therapies; Cell culture; Chemotherapy; Chinese medicine; Cytokines; DNA damage; Drug resistance; Fluorides; Genes; Laboratory animals; Lung cancer; Research Paper; Tumors; Beijing China; Australia; United States > US; China; pyroptosis; ophiopogonin B (OP-B); Caspase-1/GSDMD; drug resistant; non-small cell lung cancer (NSCLC) cells
• ISSN: 1837-9664; 1837-9664
• DOI: 10.7150/jca.66432

Drug resistance has become the main reason for the failure of tumor chemotherapy. has long been used as traditional Chinese medicine to treat pulmonary disease, and Ophiopogonin B (OP-B) as a bioactive component of it has also been verified to inhibit cell proliferation of various non-small cell lung cancer (NSCLC) cells and . Therefore, we wonder whether OP-B is also effective to drug resistant lung cancer cells. Firstly, Cell Counting Kit-8 (CCK8) assay was used to compare the sensitivity of OP-B on NCI-H460, A549, cisplatin resistant A549 (A549/DDP) and paclitaxel resistant A549 (A549/PTX) cells, and A549/DDP cells were shown to be more sensitive to OP-B than other three cell lines, the results were further verified in orthotopic tumor nude mice model and zebrafish tumor model. Moreover, observation of cell morphological feature, mitochondrial membrane potential, LDH release rate, and production of IL-1β all suggested that OP-B induced pyroptosis in A549/DDP cells more significantly than that in A549 cells. Meanwhile, transcriptomic sequencing results between OP-B treated and the Mock A549/DDP group also suggested that OP-B induced more significant Caspase-1/GSDMD dependent pyroptosis in A549/DDP group, which was further verified by VX-765, the inhibitor of Caspase-1. Together, the experimental results suggested that OP-B alleviated DDP resistance of A549 cells through inducing more significant Caspase-1/GSDMD-dependent pyroptosis.