Wang Qian, Suo Yuping, Tian Xiaojuan
Fifth Clinical Medical College, Shanxi Medical University, Taiyuan 030012, China.
Department of Gynaecology and Obstetrics, Shanxi Provincial People's Hospital, Taiyuan 030012, China.
Biomedicines. 2025 Mar 16;13(3):724. doi: 10.3390/biomedicines13030724.
: Ovarian cancer is a common gynaecological malignancy. Photodynamic therapy (PDT) mediated by 5-aminolaevulinic acid (5-ALA-PDT) is widely used in clinical practice. However, hypoxia may impact the efficacy of this treatment. In the present study, we combined the bioreductively active drug tirapazamine (TPZ) with PDT to explore its potential in enhancing ovarian cancer cell death. : A cell counting kit-8 assay was used to determine cytotoxicity under different intervention conditions. The distribution of protoporphyrin IX, a metabolite of 5-ALA, was observed using in vivo fluorescence imaging. The effect of the combined treatment was assessed by measuring changes in tumour size following the corresponding interventions and by haematoxylin and eosin staining of tumour tissues. Immunohistochemical staining was used to detect the expression levels of relevant proteins. TPZ exhibited no cytotoxicity under normoxic conditions but was activated under hypoxic conditions, inducing cytotoxic effects that were enhanced when combined with PDT. Over time, protoporphyrin IX achieved systemic distribution, and high drug concentrations were maintained within the tumour. The combination therapy suppressed tumour growth, and pathological staining showed that necrotic tumour areas were significantly enlarged after treatment. The enhanced therapeutic effect may be attributable to the inhibition of the hypoxia-inducible factor-1α/vascular endothelial growth factor axis and PI3K/Akt/mTOR pathway. : 5-ALA-PDT combined with TPZ can overcome both the hypoxic state of ovarian cancer tissues and the increased hypoxia induced by PDT, thereby inhibiting tumour growth.
卵巢癌是一种常见的妇科恶性肿瘤。由5-氨基乙酰丙酸介导的光动力疗法（5-ALA-PDT）在临床实践中被广泛应用。然而，缺氧可能会影响这种治疗的效果。在本研究中，我们将具有生物还原活性的药物替拉扎明（TPZ）与光动力疗法相结合，以探索其增强卵巢癌细胞死亡的潜力。
使用细胞计数试剂盒-8法测定不同干预条件下的细胞毒性。利用体内荧光成像观察5-ALA的代谢产物原卟啉IX的分布。通过测量相应干预后肿瘤大小的变化以及对肿瘤组织进行苏木精和伊红染色来评估联合治疗的效果。采用免疫组织化学染色检测相关蛋白的表达水平。
TPZ在常氧条件下无细胞毒性，但在缺氧条件下被激活，诱导细胞毒性作用，与光动力疗法联合时细胞毒性增强。随着时间的推移，原卟啉IX实现全身分布，肿瘤内维持高药物浓度。联合治疗抑制了肿瘤生长，病理染色显示治疗后肿瘤坏死区域明显扩大。增强的治疗效果可能归因于对缺氧诱导因子-1α/血管内皮生长因子轴和PI3K/Akt/mTOR通路的抑制。
5-ALA-PDT联合TPZ可克服卵巢癌组织的缺氧状态以及光动力疗法诱导的缺氧增加，从而抑制肿瘤生长。
