HMGA-targeted phosphorothioate DNA aptamers increase sensitivity to gemcitabine chemotherapy in human pancreatic cancer cell lines.
Elevated high mobility group A (HMGA) protein expression in pancreatic cancer cells is correlated with resistance to the chemotherapy agent gemcitabine. Here, we demonstrate use of HMGA-targeted AT-rich phosphorothioate DNA (AT-sDNA) aptamers to suppress HMGA carcinogenic activity. Cell growth of human pancreatic cancer cells (AsPC-1 and Miapaca-2) transfected with AT-sDNA were monitored after treatment with gemcitabine. Significant increases in cell death in AT-sDNA transfected cells compared to non-AT-rich sDNA treated cells were observed in both cell lines. The data indicate the potential use of HMGA targeted DNA aptamers to enhance chemotherapy efficacy in pancreatic cancer treatment.
Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, United States.
Miki
M
Watanabe
Sulaiman
S
Sheriff
Kenneth B
KB
Lewis
Stuart L
SL
Tinch
Junho
J
Cho
Ambikaipakan
A
Balasubramaniam
Michael A
MA
Kennedy
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D024003:HMGA Proteins / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D054735:Phosphorothioate Oligonucleotides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D052157:Aptamers, Nucleotide; D024003:HMGA Proteins; D054735:Phosphorothioate Oligonucleotides; D003841:Deoxycytidine; D000093542:Gemcitabine