Inhibitory effects of adenovirus-vector-mediated LRIG1 over-expression in combination with cisplatin on EJ bladder cancer cells

Abstract

Objective To investigate whether LRIG1 can facilitate cisplatin-induced bladder cancer cell lesions.Methods EJ bladder cancer cells were transfected with LRIG1 mediated by adenovirus vector.LRIG1 and epidermal growth factor receptor (EGFR) expression levels were detected in the transfected cells and compared to the untransfected cells.DNA damage,cell apoptosis,proliferation and invasion abilities were examined by single cell gel electrophoresis,flow cytometry,immunohistochemical staining and matrigel invasion assays,respectively.Results LRIG1 was up-regulated by Ad-LRIG1 transfection and EGFR was down-regulated in EJ cells.LRIG1 combined with cisplatin was responsible for severer DNA damage (OTM value,Control: 2.54 ±0.54; CDDP: 4.57 ±0.79; CDDP/Ad-GFP: 5.38 ± 1.16;CDDP/Ad-LRIGI: 9.45 ±2.64),apoptosis [apoptosis rate,control: (2.6 ±2.49)%,CDDP: (3.49 ±1.94)%,CDDP/Ad-GFP: (3.96 ± 4.68 )%,CDDP/Ad-LRIG1: ( 12.56 ± 0.77 )%],growth inhibition (cell number,control: 371.33 ± 16.17; CDDP: 224.67 ± 88.06; CDDP/Ad-GFP: 176.33 ± 69.79;CDDP/Ad-LRIG1: 138.33 ± 8.39 ) and invasion reversal ( matrigel invasion,control: 259.40 ± 9.21;CDDP: 175.00 ±25.78; CDDP/Ad-GFP: 157.20 ±22.79; CDDP/Ad-LRIG1: 114.20 ±25.11 ).Conclusion LRIG1 reduced EGFR expession and facilitated cisplatin-induced DNA damage in vitro,which might represent a novel therapeutic approach to improve the response to chemotherapy in bladder cancer. Key words: Bladder carcinoma; Epidermal growth factor receptor; Cisplatin; Chemotherapy