Breast cancer, ranking as the second leading cause of female cancer-related deaths in the U.S., demands the exploration of innovative treatments. Repurposing FDA-approved drugs emerges as an expedited and cost-effective strategy. Our study centered on proguanil, an antimalarial drug, reveals notable anti-proliferative effects on diverse breast cancer cell lines, including those derived from patients. Proguanil-induced apoptosis was associated with a substantial increase in reactive oxygen species (ROS) production, leading to reduced mitochondrial membrane potential, respiration, and ATP production. Proguanil treatment upregulated apoptotic markers (Bax, p-H2AX, cleaved-caspase 3, 9, cleaved PARP) and downregulated anti-apoptotic proteins (bcl-2, survivin) in breast cancer cell lines. In female Balb/c mice implanted with 4T1 breast tumors, daily oral administration of 20 mg/kg proguanil suppressed tumor enlargement by 55%. Western blot analyses of proguanil-treated tumors supported the in vitro findings, demonstrating increased levels of p-H2AX, Bax, c-PARP, and c-caspase3 as compared to controls. Our results collectively highlight proguanil’s anticancer efficacy in vitro and in vivo in breast cancer, prompting further consideration for clinical investigations.
乳腺癌在美国女性癌症相关死亡原因中位居第二，亟需探索创新疗法。重新利用美国食品药品监督管理局已批准药物成为一种快速且成本效益显著的策略。本研究聚焦抗疟药物氯胍，发现其对多种乳腺癌细胞系（包括源自患者的细胞系）具有显著的抗增殖作用。氯胍诱导的细胞凋亡与活性氧生成大幅增加相关，导致线粒体膜电位降低、呼吸作用减弱及ATP产量下降。在乳腺癌细胞系中，氯胍处理上调了凋亡标志物（Bax、p-H2AX、cleaved-caspase 3/9、cleaved PARP），同时下调了抗凋亡蛋白（bcl-2、survivin）表达。在植入4T1乳腺肿瘤的雌性Balb/c小鼠模型中，每日口服20 mg/kg氯胍使肿瘤生长抑制率达55%。对氯胍处理肿瘤的蛋白质印迹分析结果支持体外研究发现，显示p-H2AX、Bax、c-PARP和c-caspase3水平较对照组显著升高。本研究综合表明氯胍在乳腺癌体外及体内模型中均具有抗癌功效，值得进一步开展临床研究。
肿瘤(癌症)患者之家