title: Dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts.
abstract: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide; however, only limited therapeutic treatments are available. The aim of present study was to elucidate the therapeutic effect of dietary restriction in human NSCLC xenografts. Adult female nude mice were injected subcutaneously in the right dorsal flank with NSCLC cell line A549 cells. 5 days after tumor implantation, animals were randomly divided into ad libitum-fed group (AL, 95% of average diary intake) or dietary-restriction-fed group (DR, 70% average diary intake). 24 days after implantation, it was found that DR inhibited tumor growth marked by lower tumor volume and weight. DR suppressed tumor proliferation marked by reduced proliferating cell nuclear antigen (PCNA) expression and activated mitochondria-mediated apoptosis. DR decreased microvessel density marked by decreased CD31 immunostaining and promoted vessel maturation marked by increased alpha-smooth muscle actin (α-SMA) and reduced Factor VIII expression. DR reduced intratumoral interstitial fluid pressure and attenuated tumor hypoxia detected by EF5 immunostaining. In addition, DR suppressed NFκB signaling pathway and downregulated its downstream proteins expression including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). DR suppressed phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. In conclusion, dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts. Dietary restriction could thus be envisaged as a nutritional countermeasure against non-small-cell lung cancer.
authors.affiliation: Department of Cardiothoracic Surgery, Fuzhou General Hospital of Nanjing Command, Fuzhou 350025, China.
authors.forename: Bao-Quan
authors.initials: BQ
authors.lastname: Lin
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Zeng
authors.forename: Sheng-Sheng
authors.initials: SS
authors.lastname: Yang
authors.forename: Cong-Wen
authors.initials: CW
authors.lastname: Zhuang
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D045604:Extracellular Fluid / Q000502:physiology; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000178:diet therapy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply* / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011312:Pressure; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000199:Actins; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D005169:Factor VIII; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020155:3-Hydroxybutyric Acid