Enhanced antitumor effects by combination gene therapy using MDR1 gene shRNA and HSV1-tk in a xenograft mouse model.
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 (131)I-5-iodo-2'-fluoro-2'deoxy-1-beta-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.
Lee
Sang-Woo
SW
Department of Nuclear Medicine, Kyungpook National University, Daegu, Republic of Korea.
Lee
You La
YL
Lee
Yong Jin
YJ
Park
Seung-Yoon
SY
Kim
In-San
IS
Choi
Tae Hyun
TH
Ha
Jeoung-Hee
JH
Ahn
Byeong-Cheol
BC
Lee
Jaetae
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000628:therapy*; D004317:Doxorubicin / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D034741:RNA, Small Interfering; D001086:Arabinofuranosyluracil; C043457:fialuridine; D004317:Doxorubicin; D013937:Thymidine Kinase; D015774:Ganciclovir