title: Effective growth arrest of human colon cancer in mice, using rat sodium iodide symporter and radioiodine therapy.
abstract: We have demonstrated that the rat sodium iodide symporter (rNIS) and 131I can effectively induce growth arrest of human prostate tumor xenografts [Mitrofanova, E., Unfer, R., Vahanian, N., Daniels, W., Roberson, E., Seregina, T., Seth, P., and Link, C. (2004). Rat sodium iodide symporter (rNIS) for radioiodide therapy of cancer. Clin. Cancer Res. 10, 6969-6976]. In that study the average size of tumors established in athymic nude mice was 200 +/- 50 mm3 when treated. Testing under more rigorous and extreme in vitro conditions will better evaluate the ability of an anticancer approach to induce tumor regression or killing capacity in preclinical studies. In this work the ability of the rNIS and 131I system to inhibit the growth of relatively large (about 800 mm3 when treated with 131I) and rapidly growing colon tumors in an animal model was examined. in vitro experiments demonstrated that transduction of human colon cancer cells with Ad-rNIS resulted in a 100- to 150-fold increase in 125I uptake compared with nontransduced cells. Western blot analysis revealed robust expression of rNIS protein in cells 72-120 hr posttransduction with Ad-rNIS. Immunocytochemical analysis demonstrated that intracellular localization of rNIS-specific staining was observed mainly in plasma membranes of cells. in vitro studies revealed an immediate inhibition of growth of rapidly expanding tumors after radioiodine injection in the rNIS and 131I treatment group of mice. Twenty-seven percent of experimental mice survived more than 30 days (p = 0.019), whereas control groups had only 7% survival over 30 days. This is the first report demonstrating that rat NIS and 131I can effectively induce growth arrest of relatively large tumors in an animal model.
authors.affiliation: Iowa Cancer Research Foundation, Urbandale, IA 50322, USA. emitrofanova@iowacancer.org
authors.forename: Elena
authors.initials: E
authors.lastname: Mitrofanova
authors.forename: Robert
authors.initials: R
authors.lastname: Unfer
authors.forename: Nick
authors.initials: N
authors.lastname: Vahanian
authors.forename: Struan
authors.initials: S
authors.lastname: Kane
authors.forename: Martha
authors.initials: M
authors.lastname: Carvour
authors.forename: Charles
authors.initials: C
authors.lastname: Link
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000532:radiotherapy / Q000628:therapy; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000532:radiotherapy / Q000628:therapy; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D051381:Rats; D027981:Symporters / Q000235:genetics / Q000502:physiology*; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters