Abstract Title:

Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model.

Abstract Source:

Cancer Prev Res (Phila). 2015 Oct ;8(10):895-904. Epub 2015 Aug 14. PMID: 26276745

Abstract Author(s):

Sarah A Mazzilli, Pamela A Hershberger, Mary E Reid, Paul N Bogner, Kristopher Atwood, Donald L Trump, Candace S Johnson

Article Affiliation:

Sarah A Mazzilli

Abstract:

The chemopreventive actions of vitamin D were examined in the N-nitroso-tris-chloroethylurea (NTCU) mouse model, a progressive model of lung squamous cell carcinoma (SCC). SWR/J mice were fed a deficient diet (D) containing no vitamin D3, a sufficient diet (S) containing 2,000 IU/kg vitamin D3, or the same diets in combination with the active metabolite of vitamin D, calcitriol (C; 80μg/kg, weekly). The percentage (%) of the mucosal surface of large airways occupied by dysplastic lesions was determined in mice after treatment with a total dose of 15 or 25 μmol NTCU (N). After treatment with 15 μmol NTCU, the percentages of the surface of large airways containing high-grade dysplastic (HGD) lesions were vitamin D-deficient + NTCU (DN), 22.7% [P<0.05 compared with vitamin D-sufficient +NTCU (SN)]; DN + C, 12.3%; SN, 8.7%; and SN + C, 6.6%. The extent of HGD increased with NTCU dose in the DN group. Proliferation, assessed by Ki-67 labeling, increased upon NTCU treatment. The highest Ki-67 labeling index was seen in the DN group. As compared with SN mice, DN mice exhibited a three-fold increase (P<0.005) in circulating white blood cells (WBC), a 20% (P<0.05) increase in IL6 levels, and a four-fold (P<0.005) increase in WBC in bronchial lavages. Thus, vitamin D repletion reduces the progression of premalignant lesions, proliferation, and inflammation, and may thereby suppress development of lung SCC. Further investigations of the chemopreventive effects of vitamin D in lung SCC are warranted.

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