Table 1_Low-dose statins restore innate immune response in breast cancer cells via suppression of mutant p53.docx

BackgroundBreast cancer’s high recurrence and treatment side effects demand safer, more effective therapies. Mutations in the critical TP53 gene, which normally prevents cancer, can instead promote it. This study explores if low-dose statins can curb mutant p53 activation in breast cancer’s immune signaling, hindering tumor immune evasion.
MethodsThe study used diverse breast cancer cell lines with varying p53 statuses. Techniques included Western blot, transfection, qRT-PCR, co-immunoprecipitation, nuclear fractionation, and immunohistochemistry. In vivo experiments used BALB/c mice, with bioinformatics analysis via cBioPortal.
ResultsThe study found that suppressing mutant p53 restores innate immunity and enhances cancer treatment. Low-dose statins promoted IRF3 nuclear translocation by inhibiting mutant p53. Lovastatin treatment in vivo increased phosphorylated TBK1 and IRF3 levels and induced CD8+ T lymphocyte infiltration in tumors.
ConclusionThe findings suggest low-dose statins can enhance innate immunity in breast cancer by degrading mutant p53, offering new treatment possibilities. Caution is advised, and further research is needed to address limitations and provide solid evidence for clinical use.

背景 乳腺癌复发率高且治疗伴随诸多不良反应，亟需开发更安全、高效的治疗方案。作为关键抑癌基因的TP53（TP53），其突变反而会促进肿瘤发生发展。本研究旨在探究低剂量他汀类药物（statins）能否在乳腺癌的免疫信号通路中抑制突变型p53（mutant p53）的激活，从而阻滞肿瘤的免疫逃逸过程。
方法 本研究采用了携带不同p53状态的多种乳腺癌细胞系，所使用的实验技术包括蛋白质印迹法（Western blot）、转染、实时定量聚合酶链式反应（qRT-PCR）、免疫共沉淀（co-immunoprecipitation）、细胞核分离技术以及免疫组织化学（immunohistochemistry）。体内实验选用BALB/c小鼠，并通过cBioPortal数据库开展生物信息学分析。
结果 本研究发现，抑制突变型p53（mutant p53）可恢复固有免疫功能并提升肿瘤治疗效果。低剂量他汀类药物（statins）通过抑制突变型p53（mutant p53），促进干扰素调节因子3（IRF3）的核转位。体内洛伐他汀（Lovastatin）给药可升高磷酸化TBK1与IRF3的蛋白水平，并诱导肿瘤组织内CD8+ T淋巴细胞浸润。
结论 本研究结果表明，低剂量他汀类药物（statins）可通过降解突变型p53（mutant p53）增强乳腺癌的固有免疫应答，为临床治疗提供了新的潜在方向。但本研究仍需谨慎解读，需开展进一步研究以弥补现有局限，并为其临床应用提供坚实的证据支持。