title: Modified AS1411 Aptamer Suppresses Hepatocellular Carcinoma by Up-Regulating Galectin-14.
abstract: 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.
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Internal Medicine, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
authors: Yuri
authors: Y
authors: Cho
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Yun Bin
authors: YB
authors: Lee
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Jeong-Hoon
authors: JH
authors: Lee
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Internal Medicine, Seoul Metropolitan Government Seoul National 26 University Boramae Medical Center, Seoul, Republic of Korea.
authors: Dong Hyeon
authors: DH
authors: Lee
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Eun Ju
authors: EJ
authors: Cho
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Su Jong
authors: SJ
authors: Yu
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Yoon Jun
authors: YJ
authors: Kim
authors: Aptamer Initiative, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors: Jong In
authors: JI
authors: Kim
authors: Aptamer Initiative, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors: Jong Hun
authors: JH
authors: Im
authors: Aptamer Initiative, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors: Jung Hwan
authors: JH
authors: Lee
authors: Aptamer Initiative, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors: Eun Ju
authors: EJ
authors: Oh
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Jung-Hwan
authors: JH
authors: Yoon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052157:Aptamers, Nucleotide; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000097796:Nucleolin
chemical_list: D052157:Aptamers, Nucleotide; D037161:Galectins; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C513936:AGRO 100