Background: Breast cancer is the most prevalent cancer among women worldwide, and therapeutic resistance represents a major clinical challenge. Mitochondria are key regulators of cancer metabolism, redox homeostasis, and apoptosis, making them potential therapeutic targets. Aim: This study aimed to evaluate the effects of combined Akt and PARP inhibition on mitochondrial metabolic function, energy production, and apoptosis in breast cancer cells. Methodology: The SRB assay was used to compare the viability of MDA-MB-231 and MCF7 cells. A colony formation assay was conducted to assess the capacity of individual cells to develop colonies, and ROS production was quantified using DHR123. Flow cytometric analysis was performed to evaluate cell death, and the Seahorse Mito stress test was used to measure ATP production and essential mitochondrial parameters. Results: The combination of Akt and PARP inhibitors impaired oxidative phosphorylation without inducing a compensatory shift to glycolysis, leading to reduced ATP production, increased ROS generation, and apoptotic cell death in breast cancer cells compared to monotherapy. Conclusions and Recommendations: These findings indicate that the combination of olaparib and capivasterib is a promising therapeutic strategy for breast cancer. Furthermore, evaluation of in vivo toxicity and antitumor effectiveness is essential to validate its potential.
背景：乳腺癌是全球女性中最常见的癌症，治疗耐药性构成了主要的临床挑战。线粒体是癌症代谢、氧化还原稳态和细胞凋亡的关键调节因子，使其成为潜在的治疗靶点。目的：本研究旨在评估联合抑制Akt和PARP对乳腺癌细胞线粒体代谢功能、能量产生和细胞凋亡的影响。方法：采用SRB法比较MDA-MB-231和MCF7细胞的活力。通过集落形成实验评估单个细胞形成集落的能力，并使用DHR123定量活性氧（ROS）生成。通过流式细胞术分析评估细胞死亡，并采用Seahorse线粒体压力测试测量ATP产量及关键线粒体参数。结果：与单一疗法相比，Akt和PARP抑制剂的联合应用损害了氧化磷酸化，且未诱导向糖酵解的代偿性转变，导致乳腺癌细胞ATP产量降低、ROS生成增加并发生凋亡性细胞死亡。结论与建议：这些研究结果表明，奥拉帕尼与卡匹伐替尼的联合用药是一种有前景的乳腺癌治疗策略。此外，必须通过体内毒性和抗肿瘤效果评估来验证其潜在应用价值。
Dual Inhibition of PARP and Akt Induces Metabolic Collapse and Apoptosis in Breast Cancer Cells
肿瘤(癌症)患者之家