中国肿瘤生物治疗杂志2026，Vol.33Issue(3)：252-261,10.DOI:10.3872/j.issn.1007-385x.2026.03.004
蟾毒灵通过NLRP3/CASP1/GSDMD信号通路诱导卵巢癌细胞焦亡并增强其对顺铂的敏感性
Bufalin induces pyroptosis in ovarian cancer cells via the NLRP3/CASP1/GSDMD signaling pathway and enhances their sensitivity to cisplatin
摘要
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.关键词
卵巢癌/细胞焦亡/蟾毒灵/NLRP3/CASP1/GSDMD信号通路Key words
ovarian cancer/pyroptosis/bufalin(Buf)/NLRP3/CASP1/GSDMD signaling pathway分类
医药卫生引用本文复制引用
李婕,奚玲,赵璨..蟾毒灵通过NLRP3/CASP1/GSDMD信号通路诱导卵巢癌细胞焦亡并增强其对顺铂的敏感性[J].中国肿瘤生物治疗杂志,2026,33(3):252-261,10.基金项目
国家自然科学基金(82172717) （82172717）
