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Enhanced anti-tumor efficacy of 5-aminolevulinic acid-gold nanoparticles-mediated photodynamic therapy in cutaneous squamous cell carcinoma cells.

5-氨基酮戊酸-金纳米粒子介导的光动力疗法在皮肤鳞状细胞癌细胞中的抗肿瘤疗效增强。

  • 影响因子:1.82
  • DOI:10.1590/1414-431x20208457
  • 作者列表:"Chi YF","Qin JJ","Li Z","Ge Q","Zeng WH
  • 发表时间:2020-01-01
Abstract

:The objective of this study was to investigate whether the conjugation of gold nanoparticles (GNPs) to 5-aminolevulinic acid (5-ALA) could enhance the anti-tumor efficiency of photodynamic therapy (PDT) in epidermoid carcinoma cells. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blot, respectively. Cell viability, apoptosis, invasion, and migration were determined by MTT assay, flow cytometry, transwell invasion assay, and migration assay, respectively. Singlet oxygen generation was detected by the singlet oxygen sensor green reagent assay. Our results showed that PDT with 5-ALA and GNPs-conjugated 5-ALA (5-ALA-GNPs) significantly suppressed cell viability, increased cell apoptosis and singlet oxygen generation in both HaCat and A431 cells, and PDT with 5-ALA and 5-ALA-GNPs had more profound effects in A431 cells than that in HaCat cells. More importantly, 5-ALA-GNPs treatment potentiated the effects of PDT on cell viability, cell apoptosis, and singlet oxygen generation in A431 cells compared to 5-ALA treatment. Further in vitro assays showed that PDT with 5-ALA-GNPs significantly decreased expression of STAT3 and Bcl-2 and increased expression of Bax in A431 cells compared with PDT with 5-ALA. In addition, 5-ALA-GNPs treatment enhanced the inhibitory effects of PDT on cell invasion and migration and Wnt/β-catenin signaling activities in A431 cells compared to 5-ALA treatment. In conclusion, our results suggested that GNPs conjugated to 5-ALA significantly enhanced the anti-tumor efficacy of PDT in A431 cells, which may represent a better strategy to improve the outcomes of patients with cutaneous squamous cell carcinoma.

摘要

: 本研究的目的是研究金纳米颗粒 (GNPs) 与 5-氨基乙酰丙酸 (5-ALA) 的共轭作用。光动力疗法 (PDT) 可提高表皮样癌细胞的抗肿瘤效率。通过实时定量PCR和western blot分别测定mRNA和蛋白表达水平。分别采用MTT法、流式细胞术、transwell侵袭实验和迁移实验测定细胞活力、凋亡、侵袭和迁移。通过单线态氧传感器绿色试剂测定法检测单线态氧生成。我们的结果表明,PDT与 5-ALA和GNPs偶联的 5-ALA (5-ALA-GNPs) 显著抑制细胞活力,haCat和A431 细胞的细胞凋亡和单线态氧生成增加,5-ALA和 5-ALA-GNPs的PDT对A431 细胞的作用比HaCat细胞的作用更深远。更重要的是,与 5-ALA处理相比,5-ALA-GNPs处理增强了PDT对A431 细胞活力、细胞凋亡和单线态氧产生的影响。体外实验表明,与 5-ALA PDT相比,5-ALA-GNPs PDT可显著降低A431 细胞STAT3 和Bcl-2 的表达,增加Bax的表达。此外,与 5-ALA处理相比,5-ALA-GNPs处理增强了PDT对A431 细胞侵袭和迁移的抑制作用以及Wnt/β-catenin信号活性。总之,我们的结果表明,与 5-ALA偶联的GNPs显著增强PDT在A431 细胞中的抗肿瘤疗效,这可能是改善皮肤鳞状细胞癌患者预后的更好策略。

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影响因子:0.96
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皮肤肿瘤方向

皮肤肿瘤是发生在皮肤的细胞增生性疾病,是一种常见病。发生于皮内或皮下组织的新生物,种类很多,临床上分良性肿瘤和恶性肿瘤。恶性肿瘤可以不断增殖,引起转移,威胁生命,称为皮肤癌。

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