Drug resistance has become the main reason for the failure of
tumor chemotherapy. Radix Ophiopogon Japonicus 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 in vivo and in vitro. 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.