Skip to main content

Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA.

Publication ,  Journal Article
Kon, T; Zhang, X; Huang, Q; Yang, Z; Liu, S; Yan, B; Li, F; Wang, H; Li, C-Y
Published in: Translational cancer research
June 2012

One of the key issues in cancer radiotherapy research is to sensitize tumor cells to the cell killing effects of ionizing radiation while leaving normal tissues intact. One potential approach to achieve this is through tumor-specific targeting of DNA repair genes. In this study, we engineered a replication-deficient adenovirus encoding a mini shRNA gene targeted to the DNA-PKcs gene, which is involved in double strand break DNA repair, and evaluated its anti-tumor efficacy in combination with radiotherapy. Our shRNA-encoding adenovirus showed significant efficacy in down-regulating the levels of the DNA-PKcs protein that was accompanied by increased radiation sensitivity in the human HCT116 colon cancer cells. However, when delivered intratumorally to xenograft human tumors, minimal anti-tumor effects of the virus were seen either alone or in combination with radiation therapy, suggesting an inefficiency of the non-replicative adenovirus in delivering shRNA genes to the tumor mass. When a conditionally replicative adenovirus targeted to telomerase-positive tumor cells was used in conjunction with the DNA-PKcs-targeted shRNA-encoding non-replicative adenovirus, the efficiency of tumor-specific anti-DNA-PKcs shRNA gene expression was enhanced significantly. Most importantly, this enhanced shRNA expression led to significant anti-tumor efficacy of concurrently delivered radiation therapy. Our results suggest our shRNA-based DNA-PKcs- targeting approach in combination with tumor-targeting replicative adenovirus is a promising method to sensitize solid tumors to radiation therapy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Translational cancer research

DOI

EISSN

2219-6803

ISSN

2218-676X

Publication Date

June 2012

Volume

1

Issue

2

Start / End Page

4 / 14

Related Subject Headings

  • 3211 Oncology and carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kon, T., Zhang, X., Huang, Q., Yang, Z., Liu, S., Yan, B., … Li, C.-Y. (2012). Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA. Translational Cancer Research, 1(2), 4–14. https://doi.org/10.3978/j.issn.2218-676x.2012.05.02
Kon, Takashi, Xiuwu Zhang, Qian Huang, Zhonghui Yang, Shanling Liu, Bin Yan, Fang Li, He Wang, and Chuan-Yuan Li. “Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA.Translational Cancer Research 1, no. 2 (June 2012): 4–14. https://doi.org/10.3978/j.issn.2218-676x.2012.05.02.
Kon T, Zhang X, Huang Q, Yang Z, Liu S, Yan B, et al. Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA. Translational cancer research. 2012 Jun;1(2):4–14.
Kon, Takashi, et al. “Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA.Translational Cancer Research, vol. 1, no. 2, June 2012, pp. 4–14. Epmc, doi:10.3978/j.issn.2218-676x.2012.05.02.
Kon T, Zhang X, Huang Q, Yang Z, Liu S, Yan B, Li F, Wang H, Li C-Y. Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA. Translational cancer research. 2012 Jun;1(2):4–14.

Published In

Translational cancer research

DOI

EISSN

2219-6803

ISSN

2218-676X

Publication Date

June 2012

Volume

1

Issue

2

Start / End Page

4 / 14

Related Subject Headings

  • 3211 Oncology and carcinogenesis