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Oncol Lett. 2014 Nov;8(5):2201-2202. Epub 2014 Aug 12.

Oncolytic adenovirus-expressed RNA interference of O6-methylguanine DNA methyltransferase activity may enhance the antitumor effects of temozolomide.

Author information

1
Clinical Laboratory, The Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
2
Department of Radiotherapy, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China ; Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu 221000, P.R. China.
3
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu 221000, P.R. China.

Abstract

Temozolomide (TMZ) is an example of an alkylating agent, which are known to be effective anticancer drugs for the treatment of various solid tumors, including glioma and melanoma. TMZ acts predominantly through the mutagenic product O6-methylguanine, a cytotoxic DNA lesion. The DNA repair enzyme, O6-methylguanine DNA methyltransferase (MGMT), which functions in the resistance of cancers to TMZ, can repair this damage. RNA interference (RNAi) has been previously shown to be a potent tool for the knockdown of genes, and has potential for use in cancer treatment. Oncolytic adenoviruses not only have the ability to destroy cancer cells, but may also be possible vectors for the expression of therapeutic genes. We therefore hypothesized that the oncolytic virus-mediated RNAi of MGMT activity may enhance the antitumor effect of TMZ and provide a promising method for cancer therapy.

KEYWORDS:

O6-methylguanine DNA methyltransferase; RNA interference; alkylating agents; cancer therapy; oncolytic adenovirouses; short hairpin RNA

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