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叶绿酸辅助光动力疗法通过氧化应激诱导人宫颈癌细胞凋亡的抗癌作用。

Anti-Cancer Effect of Chlorophyllin-Assisted Photodynamic Therapy to Induce Apoptosis through Oxidative Stress on Human Cervical Cancer.

机构信息

Jeju Bio Research Center, Korea Institute of Ocean Science and Technology (KIOST), Jeju 63349, Republic of Korea.

Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan 48513, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Jul 17;24(14):11565. doi: 10.3390/ijms241411565.

Abstract

Photodynamic therapy is an alternative approach to treating tumors that utilizes photochemical reactions between a photosensitizer and laser irradiation for the generation of reactive oxygen species. Currently, natural photosensitive compounds are being promised to replace synthetic photosensitizers used in photodynamic therapy because of their low toxicity, lesser side effects, and high solubility in water. Therefore, the present study investigated the anti-cancer efficacy of chlorophyllin-assisted photodynamic therapy on human cervical cancer by inducing apoptotic response through oxidative stress. The chlorophyllin-assisted photodynamic therapy significantly induced cytotoxicity, and the optimal conditions were determined based on the results, including laser irradiation time, laser power density, and chlorophyllin concentration. In addition, reactive oxygen species generation and Annexin V expression level were detected on the photodynamic reaction-treated HeLa cells under the optimized conditions to evaluate apoptosis using a fluorescence microscope. In the Western blotting analysis, the photodynamic therapy group showed the increased protein expression level of the cleaved caspase 8, caspase 9, Bax, and cytochrome C, and the suppressed protein expression level of Bcl-2, pro-caspase 8, and pro-caspase 9. Moreover, the proposed photodynamic therapy downregulated the phosphorylation of AKT1 in the HeLa cells. Therefore, our results suggest that the chlorophyllin-assisted photodynamic therapy has potential as an antitumor therapy for cervical cancer.

摘要

光动力疗法是一种治疗肿瘤的替代方法,它利用光敏剂和激光辐射之间的光化学反应来产生活性氧。目前,由于天然光敏化合物的毒性低、副作用小、在水中的溶解度高,因此有望取代光动力疗法中使用的合成光敏剂。因此,本研究通过诱导氧化应激的凋亡反应,研究了叶绿酸辅助光动力疗法对人宫颈癌的抗癌疗效。叶绿酸辅助光动力疗法显著诱导细胞毒性,并根据结果确定了最佳条件,包括激光照射时间、激光功率密度和叶绿酸浓度。此外,在优化条件下,通过荧光显微镜检测光动力反应处理后的 HeLa 细胞中活性氧的产生和 Annexin V 的表达水平,以评估细胞凋亡。在 Western blot 分析中,光动力治疗组显示裂解的 caspase 8、caspase 9、Bax 和细胞色素 C 的蛋白表达水平增加,Bcl-2、前 caspase 8 和前 caspase 9 的蛋白表达水平受到抑制。此外,所提出的光动力治疗下调了 HeLa 细胞中 AKT1 的磷酸化。因此,我们的结果表明,叶绿酸辅助光动力疗法有望成为宫颈癌的一种抗肿瘤治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce23/10380873/c5298508b4bf/ijms-24-11565-g001.jpg

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