title: [Effects of both folic acid, p16 protein expression and their interaction on progression of cervical cancerization].
abstract: Objective:To explore the effects of both folic acid, p16 protein expression and their interaction on progression of cervical cancerization.Methods:Participants were pathologically diagnosed new cases, including 80 women with normal cervical (NC), 55 patients with low-grade cervical intraepithelial neoplasia (CINⅠ), 55 patients with high-grade cervical intraepithelial neoplasia (CINⅡ/Ⅲ) and 64 patients with cervical squamous cell carcinoma (SCC). Serum folate levels were detected by microbiological assay method while p16 protein expression levels were measured by Western-blot. In vitro, cervical cancer cell lines C33A (HPV negative) and Caski (HPV16 positive) were treated with different concentrations of folate. Proliferation and apoptosis of cells and the levels of p16 protein expression were measured in groups with different folic acid concentrations.Results:Results showed that the levels of serum folate were (5.96±3.93) ng/ml, (5.08±3.43) ng/ml, (3.92±2.59) ng/ml and (3.18±2.71) ng/ml, and the levels of p16 protein were 0.80±0.32, 1.33±0.52, 1.91±0.77, and 2.09±0.72 in the group of NC, CINⅠ, CINⅡ/Ⅲ and SCC, respectively. However, the levels of serum folate decreased (trendχ2=32.71,P<0.001) and p16 protein expression increased (trendχ2=56.06,P<0.001) gradually along with the severity of cervix lesions. An additive interaction was seen between serum folate deficiency and high expression of p16 protein in the CINⅠ, CINⅡ/Ⅲ and SCC group. Results in vitro showed that, with the increase of folate concentration, the inhibition rate of cell proliferation (C33A:r=0.928,P=0.003; Caski:r=0.962,P=0.001) and the rate on cell apoptosis (C33A:r=0.984,P<0.001; Caski:r=0.986,P<0.001) all increased but the levels of p16 protein expression (C33A:r=-0.817,P=0.025; Caski:r=-0.871,P=0.011) reduced. The proliferation inhibition rate (C33A:r=-0.935,P=0.002; Caski:r=-0.963,P=0.001) and apoptosis rate of cells (C33A:r=-0.844,P=0.017; Caski:r=-0.898,P=0.006) were negatively correlated with the levels of p16 protein expression.Conclusions:Our findings indicated that both serum folate deficiency and high expression of p16 protein could increase the risk of cervical cancer and cervix precancerous lesion, and there was an additive interaction between them. Our findings suggested that folic acid supplementation could reverse the abnormal expression of p16 protein, and effectively promote apoptosis and inhibit proliferation in cervical carcinoma cells.
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: W L
authors.initials: WL
authors.lastname: Jia
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.affiliation: Community Health Center, Shanxi Cardiovascular Hospital, Taiyuan 030001, China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Ren
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: T T
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: W M
authors.initials: WM
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: S L
authors.initials: SL
authors.lastname: Fan
authors.affiliation: Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: J T
authors.initials: JT
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018450:Disease Progression; D005260:Female; D005492:Folic Acid; D005494:Folic Acid Deficiency; D052162:Human papillomavirus 16; D006801:Humans; D002583:Uterine Cervical Neoplasms; D002578:Uterine Cervical Dysplasia
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005492:Folic Acid