Integrin α5β1 Reduces Radiosensitivity of Skin Basal Cell Carcinoma Cells

Abstract

Background: Basal cell carcinoma (BCC) is one of the common malignant epithelial tumors. Integrin α5β1 plays a crucial role in the malignant progression of various human cancers. Therefore, this study aimed to investigate the impact of Integrin α5β1 on the growth and radiosensitivity of BCC cells. Methods: The α5β1 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-α5β1 (pLEX-α5β1 subgroup), cell transfected with lentivirus containing pLEX-α5β1 and treated with 80 μmol/L Smoothened inhibitor SI4650 (pLEX-α5β1 + SI4650 subgroup). The impact of Integrin α5β1 on the cell viability was assessed utilizing Methylthiazolyldiphenyl-tetrazoliumbromide (MTT), 5-Ethynyl-2′-deoxyuridine (EdU), TdT-mediated dUTP Nick-End Labeling (TUNEL), flow cytometry, scratch assay, 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-α5β1 and then irradiated with 4 Gy X-rays (pLEX-α5β1 + 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 α5β1 were increased in the BCC cell line. Moreover, α5β1 promoted cell viability while inhibiting apoptosis in BCC cells. Furthermore, the overexpression of α5β1 promoted the Hedgehog signaling pathway. The Smoothened (SMO) inhibitor SI4650 reversed the impact of α5β1 on promoting BCC cell activity while inhibiting cell apoptosis. Additionally, α5β1 reduced the sensitivity of BCC cells to 4 Gy X-ray irradiation. Conclusion: The expression levels of α5β1 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.