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

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 experiments 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 photodynamic therapy in Colorectal Cancer through Akt inhibition.