Photodynamic therapy with TBZPy regulates the PI3K/AKT and endoplasmic reticulum stress-related PERK/eIF2α pathways in HeLa cells

Background: ((1-triphenylaminebenzo[c][1,2,5] thiadiazole-4-yl) styryl)-1-methylpyridin methylpyridin-1-ium iodide salt (TBZPy) is a novel photosensitizer that displays excellent photodynamic properties. However, There are few reports on the mechanism of action of the TBZPy photodynamic. Previous studies revealed that photodynamic therapy (PDT) could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum. Therefore, in this study, we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus (HR-HPV) infection and their underlying mechanisms. Methods: The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with TBZPy-PDT. Cell migration, invasion, and colony-forming ability were evaluated using wound-healing, Transwell invasion, and colony -forming assays, respectively. Through western blot analysis, we determined the level of expression of the PI3K/AKT and PERK/eIF2 alpha pathway proteins and the proteins associated with calcium trafficking and apoptosis. The calcium levels in the cytoplasm were detected via flow cytometry. Results: The result shows that TBZPy-PDT could inhibite the migration, invasion, and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro. And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2 alpha pathway. Moreover, TBZPy-PDT increased the levels of calcium and calmodulin, while decreasing the levels of endoplasmic reticulum calcium-binding proteins. Conclusions: TBZPy-PDT is effective on treating human papillomavirus-infected cells. Targeting the PI3K/AKT and PERK/eIF2 alpha pathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.