PT  - JOURNAL ARTICLE
AU  - Sohn Joo Ahn
AU  - Yong Jin Lee
AU  - Seung Yoon Park
AU  - You La Lee
AU  - Seon Ae Bae
AU  - Sang-Woo Lee
AU  - Jeongsoo Yoo
AU  - Byeong-Cheol Ahn
AU  - Jeoung-Hee Ha
AU  - Jaetae Lee
TI  - Improved effect of dual gene therapy with doxorubicin and I-131 by shRNA for mdr1 and NIS genes in HCT15 tumor bearing mice
DP  - 2008 May 01
TA  - Journal of Nuclear Medicine
PG  - 318P--318P
VI  - 49
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/49/supplement_1/318P.3.short
4100  - http://jnm.snmjournals.org/content/49/supplement_1/318P.3.full
SO  - J Nucl Med2008 May 01; 49
AB  - 1350 Objectives: Transduction of short hairpin RNA for mdr1 (shMDR) and NIS gene into cancer cells expressing MDR can improve therapeutic effect of anticancer therapy. We have established stable cells expressing both shMDR and NIS gene from HCT15 cells expressed MDR. In this study, we have evaluated effects of combined therapy with doxorubicin and I-131 in xenograft model of MDR human colon cancer cells (HCT15) transduced with shMDR and NIS genes. Methods: The stable cells (MN61) expressing both shRNA for mdr1 and NIS gene in HCT15 was established. Inhibition of P-gp function by shMDR was assessed by a change of Tc-99m MIBI uptake, and functional activity of NIS gene expression by a change of I-125 uptake. Doxorubicin and I-131 cytotoxicity was measured in MN61 cells or parent cells(HCT15). Tumor xenografts of MN61 and HCT15 cells were grown in nude mice and Tc-99m MIBI and I-123 images were obtained in these model. The effect of dual therapy with doxorubicin (0.5 mg/kg) and I-131 (1.5 mCi) was evaluated by serial measurement of tumor volume in vivo. Results: Cellular uptake of Tc-99m MIBI and I-125 increased to approximately 2-fold and 25-fold after transduction. MN61 cells also showed enhanced cytotoxicity by doxorubicin and I-131 compared to HCT15. Tc-99m MIBI and I-123 images demonstrated MN61 tumor were approximately 2 and 20 times higher than those in HCT15. In vivo therapy with doxorubicin, I-131, or both doxorubicin and I-131, tumor volume was significantly less that of control animals (996%, 6.4%, and 4.4% versus 1950%, respectively, P=0.05). Conclusions: Dual therapy with radioiodine and doxorubicin improves therapeutic effects after transduction of shMDR and NIS genes on colon cancer in vivo. Research Support: This work was supported by the Brain Korea 21 Project in 2008.