Effects of both folic acid, p16 protein expression and their interaction on progression of cervical cancerization
10.3760/cma.j.issn.0254-6450.2016.12.018
- VernacularTitle:叶酸与p16蛋白在宫颈癌变中的作用及其相互效应
- Author:
Wulin JIA
1
;
Ling DING
;
Zhiying REN
;
Tingting WU
;
Weimin ZHAO
;
Shilei FAN
;
Jintao WANG
Author Information
1. 山西医科大学公共卫生学院流行病学教研室
- Keywords:
Folate;
p16 protein;
Cervical carcinoma;
Interaction
- From:
Chinese Journal of Epidemiology
2016;37(12):1647-1652
- CountryChina
- Language:Chinese
-
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 (CIN Ⅰ),55 patients with high-grade cervical intraepithelial neoplasia (CIN Ⅱ/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 ofpl6 protein were 0.80 ± 0.32,1.33 ± 0.52,1.91 ± 0.77,and 2.09 ± 0.72 in the group of NC,CIN Ⅰ,CIN Ⅱ/Ⅲ and SCC,respectively.However,the levels of serum folate decreased (trend X2 =32.71,P＜ 0.001) and p 16 protein expression increased (trend x2=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 p l 6 protein in the CIN Ⅰ,CIN n/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.
