Wu Deng-Pan, Lin Tian-Yu, Bai Li-Ru, Huang Jin-Lan, Zhou Yan, Zhou Nan, Zhong Sheng-Lei, Gao Shan, Yin Xiao-Xing
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Pharmacy School of Xuzhou Medical University, Xuzhou City, Jiangsu Province, 221004, P.R. China.
Department of Pharmacology, Pharmacy School of Xuzhou Medical University, 221004, Xuzhou City, Jiangsu Province, P.R. China.
J Biophotonics. 2017 Dec;10(12):1586-1596. doi: 10.1002/jbio.201600255. Epub 2017 Apr 18.
In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26-composed gap junctional intercellular communication (GJIC) enhances the intercellular propagation of "death signal", thereby increasing chemotherapeutic cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on PDT phototoxicity. The results in the present study showed that Cx26-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx26-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid peroxide-mediated stress signaling pathways. The work presents the ability of Cx26-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that maintenance or increase of Cx26-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency. Picture: The survival response of Photofrin-PDT in Dox-treated (Cx26 expressing, GJ-formed) and Dox-untreated cells (Cx26 non-expressing, GJ-unformed) at high-cell density condition.
尽管光动力疗法（PDT）最初呈现出有前景的治疗反应，但5年复发率仍处于高水平。因此，需要提高PDT的疗效。有报道显示，由连接蛋白（Cx）26组成的间隙连接细胞间通讯（GJIC）增强了“死亡信号”的细胞间传播，从而增加化疗细胞毒性。然而，尚不清楚Cx26形成的GJIC是否对PDT光毒性有影响。本研究结果表明，高密度下由Cx26组成的GJ形成增强了卟啉钠-PDT的光毒性。当Cx26不表达或Cx26通道被阻断时，高密度培养中的光毒性显著降低，表明高密度下增强的PDT光毒性是由Cx26组成的GJIC介导的。GJIC介导的PDT光毒性增加与活性氧、钙和脂质过氧化物介导的应激信号通路有关。这项工作展示了由Cx26组成的GJIC增强恶性细胞对PDT敏感性的能力，并表明维持或增加Cx26形成的GJIC可能是提高PDT治疗效率的有效策略。图：在高细胞密度条件下，经阿霉素处理（表达Cx26，形成GJ）和未处理阿霉素的细胞（不表达Cx26，未形成GJ）中卟啉钠-PDT的存活反应。
