Connexin 43 contributes to the sensitization of colorectal cancer cells to photodynamic therapy through Akt inhibition
- Photodiagnosis Photodyn Ther. 2022 Sep;39:103040. doi: 10.1016/j.pdpdt.2022.103040.
- 1. Laboratory of Oncologic molecular medicine, Tianjin Union Medical Center, Tianjin, 300121, China.
- 2. Nankai University School of Medicine, Nankai University, Tianjin, 300121, China.
- 3. Tianjin University of Traditional Chinese Medicine, Tianjin, 300121, China.
- 4. Department of Agriculture Insect, Institute of Plant Protection, Tianjin Academy of Agricultural Sciences, Tianjin, 300381, China.
- 5. Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China.
- 6. Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China. Electronic address: [email protected].
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.