Study on the targeted therapy of oral squamous cell carcinoma with a plasmid expressing PE38KDEL toxin under control of the SERPINB3 promoter

• Main Authors: Jiang Wu, Qiong Guo, Guoliang Zhang, Liying Zhao, Yvguang Lv, Jiaqi Wang, Jiguang Liu, Wei Shi
• Format: Article
• Language: English
• Published: Wiley 2020-03-01
• Series: Cancer Medicine
• Subjects: oral squamous cell carcinoma; PE38KDEL toxin; SERPINB3 promoter; targeted therapy
• Online Access: https://doi.org/10.1002/cam4.2880

Abstract Oral squamous cell carcinoma (OSCC) has a poor prognosis and a high risk of recurrence. To improve the efficacy of OSCC therapy, it is of great significance to explore gene therapy for OSCC. The use of specific genes to regulate the targeted expression of suicide genes is a hot topic in gene therapy for cancer. The SERPINB3 gene is highly active in squamous cell carcinoma, but nearly undetectable or present at a low level in normal tissues. This specificity suggests that the SERPINB3 promoter can be used for targeted OSCC therapy. Pseudomonas aeruginosa secretes PE38KDEL, an exotoxin derivative, as a suicide gene used in gene therapy. A SERPINB3 promoter‐mediated PE38KDEL expression vector was created. The SERPINB3 gene expression was tested in different cell lines by RT‐qPCR and Western blotting, and the SERPINB3 promoter activity was detected by luciferase assay. The SERPINB3 promoter was more active in the TCA8113 cell line than in the other cell lines. The target therapeutic potential of the toxin vector pSERPINB3‐PE38KDEL was tested in the SERPINB3‐positive TCA8113 cell line, the SERPINB3‐negative MG63 cell line, and normal L02 cell line. The SERPINB3 gene was expressed at a high level in TCA8113 cells but a low level in MG63 and L02 cells. Transfection of the pSERPINB3‐PE38KDEL plasmid effectively inhibited the proliferation and invasion of TCA8113 cells and induced cell apoptosis, but no significant damage to MG63 and L02 cells was observed. The results of in vitro experiments indicated that the pSERPINB3‐PE38KDEL plasmid could be a promising strategy for targeted OSCC gene therapy.