Department of Radiotherapy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.
Department of Dermatology, the Affiliated Huai'an Hospital of Xuzhou Medical University, the Second People's Hospital of Huai'an, No.62, Huaihai Road(S.), Huai'an, 223002, China.
Anticancer Agents Med Chem. 2021;21(1):91-99. doi: 10.2174/1871520620666200814164629.
Photodynamic Therapy (PDT) is a photoactivation or photosensitization process, wherein vitamin K3 (Vit K3) serves as a photosensitizer to produce Reactive Oxygen Species (ROS) against bacteria at appropriate wavelengths. In this study, we used Vit K3 treatment combined with Ultraviolet radiation A (UVA) to produce photodynamic effects on cervical cancer.
The dose-concentration relationship between Vit K3 treatment and UVA on tumor cells was analyzed through the Cell Counting Kit-8 method. Then, the morphological characteristics of apoptosis cells were observed through fluorescent staining and fluorescence microscopy. Apoptosis after treatment with Vit K3 treatment, UVA, and Vit K3 treatment plus UVA was further observed through Western blot analysis, flow cytometry, and TUNEL assay. The xenograft models from HeLa cells were established for the exploration of the photodynamic effect of Vit K3 treatment on cervical cancer in vivo.
Vit K3 treatment plus UVA reduced tumor cell viability in a dose-dependent manner. Further studies indicated that Vit K3 treatment plus UVA can inhibit tumor growth and enhance the apoptosis of cervical cancer cells. In the combination group, the expression levels of cleaved caspase-3, cleaved caspase-9, B-cell lymphoma- extra large (Bcl-xl), and cytochrome c (cyt-c) increased obviously, whereas the expression level of Bcell lymphoma 2 (Bcl-2) decreased relative to the expression levels of UVA- or Vit K3-treated cells. In the in vivo experiments, tumor growth was inhibited significantly in the VitK3 treatment plus UVA group. Additionally, we demonstrated that the combination therapy mediated an increase in cleaved caspase-3 and cleaved caspase-9 expression and decrease in Bcl-2 expression in vivo.
Our results showed that Vit K3 treatment combined with UVA exerted photodynamic effects on cervical cancer cells by activating mitochondrial apoptosis pathways.
光动力疗法（PDT）是一种光激活或光敏化过程，其中维生素 K3（Vit K3）作为光敏剂，在适当的波长下产生活性氧物质（ROS）以对抗细菌。在这项研究中，我们使用 Vit K3 治疗联合紫外线 A（UVA）对宫颈癌产生光动力效应。
通过细胞计数试剂盒-8 法分析 Vit K3 处理与 UVA 对肿瘤细胞的剂量-浓度关系。然后，通过荧光染色和荧光显微镜观察凋亡细胞的形态特征。通过 Western blot 分析、流式细胞术和 TUNEL 检测进一步观察 Vit K3 处理、UVA 处理和 Vit K3 处理加 UVA 处理后的细胞凋亡。建立 HeLa 细胞的异种移植模型，以探索 Vit K3 治疗对宫颈癌的体内光动力效应。
Vit K3 处理加 UVA 以剂量依赖的方式降低肿瘤细胞活力。进一步的研究表明，Vit K3 处理加 UVA 可以抑制肿瘤生长并增强宫颈癌细胞的凋亡。在联合组中，裂解的 caspase-3、裂解的 caspase-9、B 细胞淋巴瘤-extra large（Bcl-xl）和细胞色素 c（cyt-c）的表达水平明显增加，而 B 细胞淋巴瘤 2（Bcl-2）的表达水平相对于 UVA 或 Vit K3 处理的细胞表达水平降低。在体内实验中，VitK3 处理加 UVA 组显著抑制肿瘤生长。此外，我们证明联合治疗介导体内裂解 caspase-3 和裂解 caspase-9 的表达增加和 Bcl-2 的表达减少。
我们的结果表明，Vit K3 处理联合 UVA 通过激活线粒体凋亡途径对宫颈癌细胞发挥光动力效应。
