INTRODUCTION Ferroptosis is involved in many types of cancers, including triple-negative breast cancer (TNBC). Suppressor of cytokine signaling 1 (SOCS1) has recently been implicated as a regulator of ferroptosis. We aim to explore whether targeting SOCS1 is a potential therapeutic strategy for TNBC therapy. METHODS Stable cell lines were constructed using lentivirus transfection. Cell viability was determined using CCK-8 and cell colony formation assays, respectively. Assays including lactate dehydrogenase release, lipid peroxidation, and malondialdehyde assays were conducted to evaluate ferroptosis. qPCR and Western blotting were performed to evaluate mRNA and protein expression, respectively. A xenograft animal model was established by subcutaneous injection of cells into the flank. RESULTS Our results showed that SOCS1 overexpression inhibited cell proliferation and induced ferroptosis in TNBC cells, while SOCS1 knockdown promoted cell proliferation and reduced ferroptosis. We also found that SOCS1 regulated ferroptosis by modulating GPX4 expression. Furthermore, SOCS1 regulated cisplatin resistance in TNBC cells by promoting ferroptosis. Our in vivo data suggested that SOCS1 regulated tumor growth and cisplatin resistance in vivo. CONCLUSION SOCS1 inhibits the progression and chemotherapy resistance of TNBC by regulating GPX4 expression.

中文翻译：

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SOCS1 作为铁死亡驱动因子，抑制三阴性乳腺癌的进展和化疗耐药性。

简介 铁死亡与许多类型的癌症有关，包括三阴性乳腺癌 (TNBC)。细胞因子信号传导抑制因子 1 (SOCS1) 最近被认为是铁死亡的调节因子。我们的目的是探讨靶向 SOCS1 是否是 TNBC 治疗的潜在治疗策略。方法采用慢病毒转染构建稳定细胞系。分别使用 CCK-8 和细胞集落形成测定法测定细胞活力。进行包括乳酸脱氢酶释放、脂质过氧化和丙二醛测定在内的测定来评估铁死亡。进行 qPCR 和 Western blotting 分别评估 mRNA 和蛋白质表达。通过向胁腹皮下注射细胞建立异种移植动物模型。结果我们的结果表明，SOCS1 过表达抑制 TNBC 细胞的细胞增殖并诱导铁死亡，而 SOCS1 敲低则促进细胞增殖并减少铁死亡。我们还发现 SOCS1 通过调节 GPX4 表达来调节铁死亡。此外，SOCS1 通过促进铁死亡来调节 TNBC 细胞的顺铂耐药性。我们的体内数据表明 SOCS1 在体内调节肿瘤生长和顺铂耐药性。结论 SOCS1通过调节GPX4的表达抑制TNBC的进展和化疗耐药。