Radiation enhances suicide gene therapy in radioresistant laryngeal squamous cell carcinoma via activation of a tumor-specific promoter.
Radioresistant cells have been shown to correlate with poor outcome after radiotherapy. Here, we found that human telomerase reverse transcriptase promoter (hTERTp) had lower activity in laryngeal squamous carcinomas cells than in radioresistant variant cells. Combining radiotherapy with plasmid phTERTp-HRP, in which expression of enzyme horseradish peroxidase (HRP) controlled by hTERTp, resulted in increased apoptosis and necrosis of tumor cells after prodrug indole-3-acetic acid (IAA; converted by HRP into a cytotoxin) incubation. Volume and wet weight of xenograft tumor were reduced more in the combination groups. These data suggest that hTERTp has potential use in targeted cancer gene therapy, especially for radioresistant tumors. Combining radiotherapy with hTERTp-HRP/IAA may overcome radioresistance in laryngeal squamous carcinomas cells and amplify the killing effect in targeted cancer cells.
Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Department of Radiochemotherapy, Zhongnan Hospital, Wuhan University, Hubei Province, Wuhan 430071, China.
Zhengkai
Z
Liao
Chenghu
C
Huang
Fuxiang
F
Zhou
Jie
J
Xiong
Jie
J
Bao
Hongyan
H
Zhang
Wenjie
W
Sun
Conghua
C
Xie
Yunfeng
Y
Zhou
D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D041722:Genes, Transgenic, Suicide / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007822:Laryngeal Neoplasms / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
C509186:TERT protein, human; D019098:Telomerase