Premium
Enhanced phototoxicity of photodynamic treatment by Cx26‐composed GJIC via ROS‐, calcium‐ and lipid peroxide‐mediated pathways
Author(s) -
Wu DengPan,
Lin TianYu,
Bai LiRu,
Huang JinLan,
Zhou Yan,
Zhou Nan,
Zhong ShengLei,
Gao Shan,
Yin XiaoXing
Publication year - 2017
Publication title -
journal of biophotonics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.877
H-Index - 66
eISSN - 1864-0648
pISSN - 1864-063X
DOI - 10.1002/jbio.201600255
Subject(s) - phototoxicity , photodynamic therapy , connexin , intracellular , chemistry , microbiology and biotechnology , calcium in biology , cytotoxicity , photosensitizer , gap junction , calcium signaling , cancer research , biophysics , biology , biochemistry , in vitro , photochemistry , organic chemistry
Abstract 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.