Modified AS1411 Aptamer Suppresses Hepatocellular Carcinoma by Up Regulating Galectin 14
Aptamers are small synthetic oligonucleotides that bind to target proteins with high specificity and affinity. AS1411 is an aptamer that binds to nucleolin, which is overexpressed in the cytoplasm and occurs on the surface of cancer cells. We investigated the therapeutic potential of aptamers in hepatocellular carcinoma (HCC) by evaluating anti tumor effects and confirming the affinity and specificity of AS1411 and modified AS1411 aptamers in HCC cells. Cell growth was assessed using the MTS assay, and cell death signaling was explored by immunoblot analysis. Fluorescence activated cell sorting was performed to evaluate the affinity and specificity of AS1411 aptamers in SNU 761 HCC cells. We investigated the in vivo effects of the AS1411 aptamer using BALB/c nude mice in a subcutaneous xenograft model with SNU 761 cells. Treatment with a modified AS1411 aptamer significantly decreased in vitro (under normoxic [P 0.035] and hypoxic [P 0.018] conditions) and in vivo (under normoxic conditions, P 0.041) HCC cell proliferation compared to control aptamers. AS1411 and control aptamers failed to control HCC cell proliferation. However, AS1411 and the modified AS1411 aptamer did not induce caspase activation. Decrease in cell growth by AS1411 or modified AS1411 was not prevented by caspase or necrosis inhibitors. In a microarray, AS1411 significantly enhanced galectin 14 expression. Suppression of HCC cell proliferation by the modified AS1411 aptamer was attenuated by galectin 14 siRNA transfection. Modified AS1411 aptamer suppressed HCC cell growth in vitro and in vivo by up regulating galectin 14 expressions. Modified AS1411 aptamers may have therapeutic potential as a novel targeted therapy for HCC.
PloS one