Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Biomed Pharmacother. 2024 Aug;177:117110. doi: 10.1016/j.biopha.2024.117110. Epub 2024 Jul 14.
Photodynamic therapy (PDT), employing photosensitizers to induce formation of reactive oxygen species (ROS) for tumor elimination, is emerging as a promising treatment modality in oncology due to its unique benefits. However, the PDT application in ovarian cancer, the most prevalent and lethal type of gynecological malignancy with a severe hypoxic microenvironment, remains unknown. This study revealed that photosensitizer TMPyP4 exhibited enhanced efficacy under HO stimulation, with minimal change in cytotoxicity compared to TMPyP4 alone. The results showed that HO increased ROS production induced by TMPyP4, leading to exacerbated mitochondrial dysfunction and DNA damage, ultimately inhibiting proliferation and inducing apoptosis in ovarian cancer cells. Mechanistically, HO primarily enhanced the therapeutic efficacy of PDT with TMPyP4 against ovarian cancer cells by degrading HIF-1α, which subsequently modulated the HIF-1 signaling pathway, thereby alleviating the hypoxic environment in ovarian cancer cells. Our findings underscore the therapeutic potential of targeting HIF-1α within the hypoxic microenvironment for PDT in ovarian cancer and propose a novel integrated strategy for PDT treatment of this malignancy in vitro.
光动力疗法（PDT）利用光敏剂诱导活性氧（ROS）的形成来消除肿瘤，由于其独特的优势，正在成为肿瘤学中一种有前途的治疗方式。然而，在卵巢癌中的 PDT 应用仍然未知，卵巢癌是最常见和致命的妇科恶性肿瘤，具有严重的缺氧微环境。本研究表明，在 HO 刺激下，光敏剂 TMPyP4 的效果增强，与单独使用 TMPyP4 相比，细胞毒性变化不大。结果表明，HO 增加了 TMPyP4 诱导的 ROS 产生，导致线粒体功能障碍和 DNA 损伤加剧，最终抑制卵巢癌细胞的增殖并诱导其凋亡。从机制上讲，HO 通过降解 HIF-1α 主要增强了 TMPyP4 对卵巢癌细胞的 PDT 疗效，从而调节了 HIF-1 信号通路，从而减轻了卵巢癌细胞的缺氧环境。我们的研究结果强调了针对缺氧微环境中的 HIF-1α 进行 PDT 治疗卵巢癌的治疗潜力，并提出了一种用于该恶性肿瘤体外 PDT 治疗的新的综合策略。
