OR35-6 INHIBITION OF HUMAN COLON CANCER CELL PROLIFERATION IN VITRO AND XENOGRAFT GROWTH BY NANOPARTICULATE TETRAIODOTHYROACETIC ACID (NANOTETRAC)

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR35-Neoplasia of Endocrine Tissues
Bench to Bedside
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 12:30 PM
Room 122 (Moscone Center)
Hung-Yun Lin*1, Shaker Mousa1, Murat Yalcin1, Heng Yuan Tang1, Mary Koeppe Luidens2, Faith B Davis1 and Paul J Davis3
1Albany College of Pharmacy and Health Sciences, Rensselaer, NY, 2Albany Medical Center, Albany, NY, 3Albany College of Pharmacy and Health Sciences
The deaminated analogue of L-thyroxine, tetraiodothyroacetic acid (tetrac) and its poly[lactic-co-glycolic] acid nanoparticle formulation, Nanotetrac (NP-Tetrac), act at a receptor on plasma membrane integrin αvβ3 of human cancer cells and dividing blood vessel cells to inhibit cell proliferation and xenograft growth.  NP-tetrac does not enter cells and acts exclusively at the integrin.  NP-tetrac inhibited proliferation in vitro of Colo205 (wild-type KRAS) cells and chemoresistant KRAS-mutant (HCT116) human colon carcinoma cells.  Cetuximab, a monocloncal antibody to epidermal growth factor receptor (EGFR), is widely used clinically against colorectal cancer bearing wild-type KRAS; cetuximab suppressed proliferation of Colo205 cells and was confirmed to be ineffective against HCT116 cells.  Combination low-concentration cetuximab and NP-tetrac was more effective in vitro than NP-tetrac, alone, suggesting chemosensitization by NP-tetrac that has been described by us in other cell lines.  We also compared effectiveness of NP-tetrac and cetuximab, alone or in combination, against xenografts of Colo205 cells in nude mice.  Study duration of 8 d was determined by growth of tumors in control aniamls to a size (2.0 gm) requiring animal sacrifice.  NP-tetrac (0.1 mg/kg i.p. daily) was administered, with or without cetuximab (0.1 or 1.0 mg/kg i.p. every 2 d).  Tumor size was measured daily.  In preliminary studies, control tumors increased in volume  by 2.7 -fold from a baseline of 700 mm3.  Administered individually, cetuximab and NP-tetrac, each at 0.1 mg/kg, permitted increases in tumor size of 0.4-fold to 0.7 fold, a mean reduction vs. control of 80%.  Combination drug therapy in Colo205 xenografts was not additive.  In summary, study results in mutant KRAS HCT116 cell in vitro suggest sensitivity to cetuximab is restored by low-dose NP-tetrac.  Cetuximab and NP-tetrac, individually, are equally effective suppressors of human wild-type KRAS-bearing Colo205 xenografts.

Nothing to Disclose: HYL, SM, MY, HYT, MKL, FBD, PJD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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