High mobility group A1 (HMGA1) is family of DNA binding proteins found to be highly expressed in cancer cells.  HMGA1 proteins acts as an architectural transcription factors to control gene expressions by binding to the minor groove of AT-rich DNA with its characteristic AT-hooks.  The overexpression of HMGA in cancers has been recognized to cause gemcitabine based chemotherapy resistance and prevent apoptosis of pancreatic cancer cells.  Based on our knowledge of HMGA1 activity, we have designed AT-rich phosphorothioate DNA (AT-sDNA) to act as inhibitors of HMGA1 protein's oncogenic  activity and restore sensitivity to chemotherapy.  We hypothesized, combined with gemcitabine treatment, AT-rich DNA transfection will decrease the cell viability dramatically.  Human pancreatic cancer cell line AsPC-1, were transfected with AT-sDNA.  The change in the sensitivity to gemcitabine treatment after sDNA transfection was examined be cell viability assay.  This study demonstrated the potential use of DNA analogs as HMGA1 targeted cancer treatment.

HMGA1 targeted phosphorothioate DNA increases the sensitivity to chemotherapy reagent in pancreatic cancer cell line

241st National Meeting (2011)

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