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Archive > Volume 33 Issue 3 > 2026,33(3):252-261. DOI:10.3872/j.issn.1007-385X.2026.03.004 Prev Next
Basic Research
Bufalin induces pyroptosis in ovarian cancer cells via the NLRP3/CASP1/GSDMD signaling pathway and enhances their sensitivity to cisplatin
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Abstract:
[Abstract] Objective: To investigate the cytotoxic effects and underlying mechanisms of Bufalin (Buf) on ovarian cancer cells (A2780 and SKOV3) and to evaluate its synergistic cytotoxicity with cisplatin (DDP). Methods: A2780 and SKOV3 cells were routinely cultured. The effect of Buf on cell proliferation and its half-maximal inhibitory concentration (IC50) were determined using CCK-8 assay and colony formation assay. Following treatments with various concentrations of Buf, morphological changes of tumor cells were observed under a microscope, lactate dehydrogenase (LDH) release was measured using colorimetric assay, and the proportion of Annexin Ⅴ?PI? cells was analyzed using flow cytometry. The mRNA and protein expression levels of pyroptosis-related molecules were detected using qPCR and WB, respectively. Small interfering RNA was used to knock down gasdermin D (GSDMD) in A2780 and SKOV3 cells to validate its functional role. The synergistic cytotoxic effects of Buf and DDP against A2780 and SKOV3 cells were analyzed using the SynergyFinder platform, and the underlying mechanisms were further explored using flow cytometry, qPCR, and WB. Additionally, the synergistic effect of Buf and DDP on DDP-resistant A2780 and SKOV3 cells was evaluated using flow cytometry. Results: Compared with the control group, Buf significantly inhibited proliferation and migration of ovarian cancer cells (both P < 0.05), induced LDH release and cell pyroptosis (both P < 0.05), and upregulated the mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), cysteine-aspartic acid protease 1 (CASP1), gasdermin D (GSDMD), interleukin(IL) -1β, and IL-18 (all P < 0.05). The combination of Buf and DDP synergistically inhibited the proliferation of A2780 and SKOV3 cells and further enhanced the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP. Conclusion: Buf induces pyroptosis in A2780 and SKOV3 cells by activating the NLRP3/CASP1/GSDMD signaling pathway and enhances the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP.
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