Journal
JOURNAL OF BIOPHOTONICS
Volume 10, Issue 12, Pages 1586-1596Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/jbio.201600255
Keywords
photodynamic therapy; Gap junctional intercellular communication; Connexin26; phototoxicity
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Funding
- Natural Science Foundation of China [81402946]
- Xuzhou Medical University, China [D2014017, D2014010]
- Natural Science Research grant of Higher Education of Jiangsu province, China [14KJD310002]
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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.
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