OBJECTIVE Breast cancer is the most common and high-incidence cancer in women. It is mainly treated by surgery combined with chemoradiation. The main challenge in treating breast cancer patients is developing resistance to chemotherapeutics, so it is urgent to find potential strategies that can improve the chemotherapy effect of patients. In this study, we aimed to explore the role of GSDME methylation in the sensitivity of chemotherapy for breast cancer. METHODS Here, we identified breast cancer MCF-7 / Taxol cells models using quantitative real-time PCR (qRT-PCR), Western blotting (WB), and cell counting kit-8 (CCK-8) analyses. Epigenetic changes in it were detected by Methylated DNA immunoprecipitation-sequencing and methylation-specific PCR. The expression level of GSDME in breast cancer cells was observed by qPCR and WB analyses. CCK-8 and colony formation assay were used to detect cell proliferation. Finally, pyroptosis was detected by LDH assay, flow cytometry, and WB analyses. RESULTS Our results indicate that ABCB1 mRNA and p-GP expression are significantly increased in breast cancer MCF-7 / Taxol cells. GSDME enhancer methylation was found in drug-resistant cells and was associated with the down-regulation of GSDME expression. After treatment with decitabine (5-Aza-2'-deoxycytidine), the demethylation of GSDME induced the occurrence of pyroptosis and thereby inhibited the proliferation of MCF-7 / Taxol cells. We found that the upregulation of GSDME enhances the chemosensitivity of MCF-7 / Taxol cells to paclitaxel by inducing pyroptosis. CONCLUSION Taken together, we identified decitabine increases GSDME expression through DNA demethylation and induces pyroptosis, thus increasing the chemosensitivity of MCF-7 / Taxol cells to Taxol. Use of decitabine / GSDME / pyroptosis-based treatment strategies may be a new way to overcome the resistance of breast cancer to paclitaxel chemotherapy.

中文翻译：

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通过 DNA 去甲基化促进 GSDME 表达，提高乳腺癌 MCF-7/Taxol 细胞的化疗敏感性。

目的乳腺癌是女性中最常见且高发的癌症。主要采用手术结合放化疗的治疗方法。治疗乳腺癌患者的主要挑战是对化疗药物产生耐药性，因此迫切需要找到可以改善患者化疗效果的潜在策略。在本研究中，我们旨在探讨GSDME甲基化在乳腺癌化疗敏感性中的作用。方法在这里，我们使用定量实时 PCR (qRT-PCR)、蛋白质印迹 (WB) 和细胞计数试剂盒 8 (CCK-8) 分析鉴定了乳腺癌 MCF-7/紫杉醇细胞模型。通过甲基化DNA免疫沉淀测序和甲基化特异性PCR检测其表观遗传变化。通过qPCR和WB分析观察乳腺癌细胞中GSDME的表达水平。CCK-8和集落形成实验用于检测细胞增殖。最后，通过 LDH 测定、流式细胞术和 WB 分析检测细胞焦亡。结果我们的结果表明乳腺癌MCF-7 /紫杉醇细胞中ABCB1 mRNA和p-GP表达显着增加。在耐药细胞中发现了 GSDME 增强子甲基化，并与 GSDME 表达下调相关。地西他滨（5-Aza-2'-脱氧胞苷）处理后，GSDME的去甲基化诱导细胞焦亡的发生，从而抑制MCF-7/Taxol细胞的增殖。我们发现GSDME的上调通过诱导细胞焦亡增强MCF-7/Taxol细胞对紫杉醇的化疗敏感性。结论 综上所述，我们发现地西他滨通过 DNA 去甲基化增加 GSDME 表达并诱导细胞焦亡，从而增加 MCF-7/Taxol 细胞对紫杉醇的化疗敏感性。使用地西他滨/GSDME/焦亡为主的治疗策略可能是克服乳腺癌对紫杉醇化疗耐药的新途径。