Radiosensitive gene therapy through imRNA expression for silencing manganese superoxide dismutase.
BACKGROUND
In radiotherapy, therapeutic efficacy for the control of cancer is often limited by tumor tissue radioresistance including nasopharyngeal carcinoma. Exposure of cells to ionizing radiation (IR) leads to the formation of reactive oxygen species that are associated with radiation-induced cellular apoptosis and necrosis. The antioxidant enzyme manganese superoxide dismutase (SOD2) catalyzes the dismutation of the superoxide anions into hydrogen peroxide.


METHODS
We have investigated the potential of SOD2 gene silencing, through plasmid transfer using a microRNA interference optimized for transcription in nasopharyngeal carcinoma cell line cells, to degrade the radioresistance of a human nasopharyngeal carcinoma cell line. Using these as in vitro models we have investigated whether SOD2 gene therapy may be suitable for the reduction of the nasopharyngeal carcinoma resistance to the effects of IR.


RESULTS
Here we demonstrate using both biological and physical assays that silencing of SOD2 enhances the radiosensitivity of nasopharyngeal carcinoma cells to IR injury. Our results show that a decrease in the levels of SOD2 mRNA and protein within CNE1 cells (down-regulated 65 and 80%) leads to a significant decrease in clonogenic survival (from 24.5 to 9.67% at 2 Gy, from 9.12 to 2.45% at 4 Gy), as evident by a significant decrease in Dbar (from 1.923 to 0.617 Gy), SF(2) (from 0.403 to 0.021) values, and a significant increase in the alpha value (from 0.228 +/- 0.070 to 1.064 +/- 0.210/Gy) when compared either to cells transduced with a Gateway-adapted expression vector encoding EmGFP alone or to the parental line.


CONCLUSIONS
The results presented suggest that miRNA for silencing SOD2 radiosensitizing gene therapy maybe applicable to the nasopharyngeal carcinoma, improving the therapeutic ratio of cancer radiotherapy.
Qu
Yaming
Y
Department of Otolaryngology Head and Neck Surgery, Xiang Ya Hospital, Central South University, 410008 Changsha, China.
Zhao
Suping
S
Hong
Jidong
J
Tang
Sane
S
D001483:Base Sequence; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D035683:MicroRNAs; D013482:Superoxide Dismutase