Wu Deng-Pan, Bai Li-Ru, Lv Yan-Fang, Zhou Yan, Ding Chun-Hui, Yang Si-Man, Zhang Fan, Wang Yuan-Yuan, Huang Jin-Lan, Yin Xiao-Xing
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Pharmacy School of Xuzhou Medical University, Xuzhou, China.
Department of Pharmacology, Pharmacy School of Xuzhou Medical University, Xuzhou, China.
Front Oncol. 2019 Jul 9;9:595. doi: 10.3389/fonc.2019.00595. eCollection 2019.
Despite responses to initial treatment of photodynamic therapy (PDT) being promising, a recurrence rate exists. Thus, finding novel therapeutic targets to enhance PDT efficacy is an urgent need. Reports indicate that connexin (Cx) 40 plays an important role in tumor angiogenesis and growth. However, it is unknown whether Cx40-composed channels have effects on PDT efficacy. The study uniquely demonstrated that Cx40-formed channels could enhance the phototoxicity of PDT to malignant cells and . Specifically, Cx40-formed channels at high cell density could increase PDT photocytotoxicity. This action was substantially restricted when Cx40 expression was not induced or Cx40 channels were restrained. Additionally, the presence of Cx40-composed channels enhanced the phototoxicity of PDT in the tumor xenografts. The above results indicate that enhancing the function of Cx40-formed channels increases PDT efficacy. The enhancement of PDT efficacy mediated by Cx40 channels was related with intracellular pathways mediated by ROS and calcium pathways, but not the lipid peroxide-mediated pathway. This work demonstrates the capacity of Cx40-mediated channels to increase PDT efficacy and suggests that therapeutic strategies designed to maintain or enhance Cx40 expression and/or channels composed by Cx40 may increase the therapeutic efficacy of PDT.
尽管光动力疗法（PDT）初始治疗的反应很有前景，但仍存在复发率。因此，寻找新的治疗靶点以提高PDT疗效迫在眉睫。报告表明，连接蛋白（Cx）40在肿瘤血管生成和生长中起重要作用。然而，由Cx40组成的通道是否对PDT疗效有影响尚不清楚。该研究独特地证明，Cx40形成的通道可增强PDT对恶性细胞的光毒性。具体而言，在高细胞密度下Cx40形成的通道可增加PDT的光细胞毒性。当未诱导Cx40表达或抑制Cx40通道时，这种作用会受到很大限制。此外，由Cx40组成的通道的存在增强了PDT在肿瘤异种移植中的光毒性。上述结果表明，增强Cx40形成的通道的功能可提高PDT疗效。由Cx40通道介导的PDT疗效增强与由活性氧（ROS）和钙途径介导的细胞内途径有关，但与脂质过氧化物介导的途径无关。这项工作证明了Cx40介导的通道提高PDT疗效的能力，并表明旨在维持或增强Cx40表达和/或由Cx40组成的通道的治疗策略可能会提高PDT的治疗效果。
