Preclinical validation of talaporfin sodium-mediated photodynamic therapy for esophageal squamous cell carcinoma.

Preclinical validation of talaporfin sodium-mediated photodynamic therapy for esophageal squamous cell carcinoma.
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DOI:
10.1371/journal.pone.0103126
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Muto M
Muto M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ohashi S;Kikuchi O;Tsurumaki M;Nakai Y;Kasai H;Horimatsu T;Miyamoto S;Shimizu A;Chiba T;Muto M

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光动力疗法(PDT)通过致癌光敏剂介导的光化学反应杀死癌细胞。在此,我们进行了一项实验性的临床前研究,以验证他拉普芬钠介导的光动力疗法(t-PDT)对食管鳞状细胞癌(ESCC)细胞的抗肿瘤作用。我们使用了来自不同分化级别或对5-氟尿嘧啶(5-FU)耐药的人ESCC细胞。通过检测细胞存活率、细胞凋亡率、细胞内活性氧(ROS)生成和DNA双链断裂来确定t-PDT的细胞毒作用。此外,通过锚定非依赖细胞生长实验和异种移植模型评估了t-PDT的抗肿瘤作用。T-PDT对ESCC细胞具有较强的细胞毒作用,不受分化程度和5-FU耐药性的影响。此外,t-PDT诱导强大的细胞凋亡,表现为细胞萎缩、核周空泡化、核碎裂和诱导Annexin V阳性细胞。这种凋亡反应伴随着ROS的同时激活和DNA双链断裂的诱导。重要的是,t-PDT有效地抑制了非贴壁细胞生长以及ESCC异种移植瘤的形成。总之,t-PDT对不同组织学分级或化疗耐药的ESCC细胞显示出抗肿瘤的潜力,为t-PDT治疗ESCC提供了一种新的翻译原理。
Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.
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