Combined adenine nucleotide translocator 2 (ANT2) shRNA therapy and hNIS radionuclide gene therapy in mouse model of colon cancer

Objectives Recently, we reported on the anti-tumor effects of vector-based ANT2 shRNA therapy in human breast cancer model. In this study, we investigated the therapeutic effects of combined ANT2 shRNA therapy and hNIS radionuclide gene therapy in mouse colon cancer cells.

Methods Mouse colon cancer cells expressing hNIS (CT26/hNIS) were treated with HBSS, ANT2 scramble vector (AS), ANT2 shRNA vector (AR), I-131, ANT2 scramble vector + I-131 (ASI), and ANT2 shRNA vector + I-131 (ARI) using Lipofectamine 2000 and I-131 (300 uCi/5 mL). Twenty-four hours later, apoptotic cell death rates (%), I-125 uptake, and the levels of MHC class I and Fas gene expression were measured in various groups of CT26/hNIS cells using a gamma counter and FACS analysis.

Results The rates of apoptotic cell death were 0.1, 0.1, 22.1, 14, 10.5, 43.1% in HBSS, AS, AR, I-131, ASI, and ARI group, respectively. ARI group showed the least uptake of I-125 among six groups. The levels of MHC class I expressing cancer cells were 11.9, 12.7, 17.6, 59.3, 58, and 75% in HBSS, AS, AR, I-131, ASI, and ARI group, respectively. The percentage of Fas expressing cancer cells were 5.7, 6.8, 20.6, 17.9, 16.8, and 49.9% in HBSS, AS, AR, I-131, ASI, and ARI group, respectively.

Conclusions Our data suggest that combined vector-based ANT2 shRNA therapy and hNIS radionuclide gene therapy could be an effective therapeutic method for cancer treatment.