Integrin α5β1 Reduces Radiosensitivity of Skin Basal Cell Carcinoma Cells

Background: Basal cell carcinoma (BCC) is one of the common malignant epithelial tumors. Integrin alpha 5 beta 1 plays a crucial role in the malignant progression of various human cancers. Therefore, this study aimed to investigate the impact of Integrin alpha 5 beta 1 on the growth and radiosensitivity of BCC cells. Methods: The alpha 5 beta 1 mRNA concentration in normal human epidermal keratinocytes PCS-200-11 and human skin BCC cell lines (TE354.T and A431) was appraised using Reverse Transcription Polymerase Chain Reaction (RT-qPCR). The cells were randomly divided into the normal cell culture (control subgroup), cells transfected with lentivirus containing pLEX-Multiple Cloning Site (MCS) (pLEX-MCS subgroup), cells transfected with lentivirus containing pLEX-alpha 5 beta 1 (pLEX-alpha 5 beta 1 subgroup), cell transfected with lentivirus containing pLEX-alpha 5 beta 1 and treated with 80 mu mol/L Smoothened inhibitor SI4650 (pLEX-alpha 5 beta 1 + SI4650 subgroup). The impact of Integrin alpha 5 beta 1 on the cell viability was assessed utilizing Methylthiazolyldiphenyl-tetrazoliumbromide Transwell migration, and Transwell invasion assays. Furthermore, the TE354.T cells and A431 cells were randomly divided into the normal cell culture (control subgroup), cells were irradiated with 4 Gray (Gy) X-rays (4 Gy subgroup), and cell transfected with lentivirus containing pLEX-alpha 5 beta 1 and then irradiated with 4 Gy X-rays (pLEX-alpha 5 beta 1 + 4 Gy subgroup). The cell viability of BCC cells was determined using MTT and flow cytometry analysis. Additionally, the Hedgehog signaling pathway-related proteins were evaluated using western blot analysis. Results: The expression levels of alpha 5 beta 1 were increased in the BCC cell line. Moreover, alpha 5 beta 1 promoted cell viability while inhibiting apoptosis in BCC cells. Furthermore, the overexpression of alpha 5 beta 1 promoted the Hedgehog signaling pathway. The Smoothened (SMO) inhibitor SI4650 reversed the impact of alpha 5 beta 1 on promoting BCC cell activity while inhibiting cell apoptosis. Additionally, alpha 5 beta 1 reduced the sensitivity of BCC cells to 4 Gy X-ray irradiation. Conclusion: The expression levels of alpha 5 beta 1 were elevated in BCC cells, resulting in enhanced cell viability, abated apoptosis, and alleviated sensitivity to radiotherapy. This mechanism of action may be linked to the Hedgehog signaling pathway.