Connexin 43 contributes to the sensitization of colorectal cancer cells to photodynamic therapy through Akt inhibition

文献类型： 外文期刊

第一作者： Wang, Yijia

作者： Wang, Yijia;Zhu, Siwei;Chen, Lankai;Lai, Sizhen;Liu, Yanfei;Yi, Ben;Hu, Xia;Zhang, Qinghuai;Zhang, Chunze

作者机构： Tianjin Union Med Ctr, Lab Oncol Mol Med, Tianjin 300121, Peoples R China;Nankai Univ, Sch Med, Tianjin 300121, Peoples R China;Tianjin Univ Tradit Chinese Med, Tianjin 300121, Peoples R China;Tianjin Acad Agr Sci, Inst Plant Protect, Dept Agr Insect, Tianjin 300381, Peoples R China;Tianjin Union Med Ctr, Dept Colorectal Surg, Tianjin 300121, Peoples R China

关键词： Photodynamic Therapy; Resistance; Akt activation; Connexin 43

期刊名称：PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY （ 2022影响因子：3.3； 五年影响因子：3.3 ）

ISSN： 1572-1000

年卷期： 2022 年 39 卷

页码：

收录情况： SCI

摘要： Background: Photodynamic therapy could be one approach to treat colorectal cancer though resistance leads to failure of therapy. Akt activation is a cellular survival response to photodynamic therapy and is also a reason for resistance. Thus, inhibition of Akt is a strategy to decrease resistance. Akt interacts with connexin 43, another protein involved in photodynamic therapy resistance. Connexin 43 is widely expressed in different human tissues and has a complex role in tumor development. However, the mechanism of inhibition of Akt by connexin 43 that sensitizes colorectal cancer cells to photodynamic therapy needs further investigation. Methods: In this study, two colorectal cancer cells with low phosphorylated connexin 43 level were used to explore this mechanism. LY294002 was used as an Akt inhibitor, and connexin 43-pCMV3 was transfected into cells to increase connexin 43 expression. Results: Akt and connexin 43 inhibit each other in both colorectal cancer cell lines. In vitro and in vivo exper-iments showed that LY294002 and connexin 43 transfection sensitized cells to hematoporphyrin-Photodynamic therapy. LY294002 increased the sensitivity of cells to photodynamic therapy with a pronounced effect in cells with high expression levels of connexin 43. Conclusions: Connexin 43 should be considered an important factor in increasing the phototoxicity of photody-namic therapy in colorectal cancer through Akt inhibition.

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