Enhanced antitumor effects by combination gene therapy using MDR1 gene shRNA and HSV1-tk in a xenograft mouse model

Sang Woo Lee, You La Lee, Yong Jin Lee, Seung Yoon Park, In San Kim, Tae Hyun Choi, Jeoung Hee Ha, Byeong Cheol Ahn, Jaetae Lee

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

The use of a novel therapeutic vector containing HSV1-thymidine kinase (HSV1-tk) and a short hairpin RNA for the MDR1 gene (shMDR) was proposed previously. We investigated the antitumor effects in an in vivo mouse model of colon cancer and assessed treatment response by serial non-invasive imaging. shMDR-TK expressing (MTKG) tumors for the dual therapy group mice with ganciclovir and doxorubicin showed a decrease in size, while tumors in the single therapy group mice showed a moderate increase (p < 0.05). The 131I-5-iodo-2′-fluoro-2′deoxy-1-β-d-arabinofuranosyluracil (FIAU) uptake ratio of MTKG-to-parent HCT-15 tumors decreased as treatment progressed for single or dual therapy group mice, while that of the control group mice increased gradually. This study demonstrates the enhanced antitumor effects with combination gene therapy compared with a single therapeutic approach, and provides the potential of therapeutic response monitoring.

Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalCancer letters
Volume291
Issue number1
DOIs
Publication statusPublished - 2010 May 1
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a Grant from the advanced medical technology cluster for diagnosis and prediction at Kyungpook National University from Ministry of Knowledge Economy, Nuclear Research & Development Program of National Research Foundation of Korea funded by Ministry of Education, Science & Technology (Grant code: 2009-0078234) and Brain Korea 21 from Ministry of Education, Science and Technology, Republic of Korea.

Keywords

  • Combination gene therapy
  • HSV1-tk
  • I-FIAU imaging
  • MDR1
  • shRNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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