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

文献类型: 外文期刊

作者: Wang, Yijia 1 ; Chen, Lankai 2 ; Lai, Sizhen 3 ; Liu, Yanfei 3 ; Yi, Ben 3 ; Zhu, Siwei 1 ; Hu, Xia 4 ; Zhang, Qinghuai 5 ; Zhang, Chunze 5 ;

作者机构: 1.Tianjin Union Med Ctr, Lab Oncol Mol Med, Tianjin 300121, Peoples R China

2.Nankai Univ, Sch Med, Tianjin 300121, Peoples R China

3.Tianjin Univ Tradit Chinese Med, Tianjin 300121, Peoples R China

4.Tianjin Acad Agr Sci, Inst Plant Protect, Dept Agr Insect, Tianjin 300381, Peoples R China

5.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 ( 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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