Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model.
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; 80 μg/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.
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York. Mazzilli@bu.edu.
Sarah A
SA
Mazzilli
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York.
Pamela A
PA
Hershberger
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
Mary E
ME
Reid
Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York.
Paul N
PN
Bogner
Department of Biostatistics, Roswell Park Cancer Institute, Buffalo New York.
Kristopher
K
Atwood
Inova Health System, Falls Church, Virginia.
Donald L
DL
Trump
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York.
Candace S
CS
Johnson
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000473:pathology*; D002762:Cholecalciferol / Q000378:metabolism / Q000494:pharmacology*; D004032:Diet; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000150:complications / Q000473:pathology*; D051379:Mice; D060885:Multiplex Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D014808:Vitamin D Deficiency / Q000150:complications*
D016588:Anticarcinogenic Agents; D002762:Cholecalciferol