叶酸水平及HPV16感染对妇女发生宫颈癌变的协同作用研究  

Study of Synergistic Effect of Folate Levels and HPV16 Infection on Cervical Carcinogenesis

作　　者：许晓燕 邢辉[2] 兰艳丽[2] 刘韵[2] 

机构地区：[1]武汉市江夏区第一人民医院,430200 [2]襄阳市中心医院,441021

出　　处：《实用癌症杂志》2016年第6期875-878,共4页The Practical Journal of Cancer

基　　金：湖北省卫生计生委基金项目(编号:WJ2015MA024)

摘　　要：目的探讨叶酸水平、HPV16感染及HPV16 E2和E6 mRNA水平与宫颈癌变的关系,并研究叶酸水平及HPV16感染在宫颈癌变中的协同作用。方法选择新发宫颈炎症(CI)患者40例、宫颈上皮内瘤样变(CIN)患者80例(CINⅠ患者36例,CINⅡ/Ⅲ44例)、宫颈鳞状细胞癌(SCC)患者48例作为研究对象,采用微生物法测定血清叶酸和红细胞叶酸含量,采用PCR检测宫颈癌组织HPV16的感染情况,采用荧光定量PCR检测宫颈癌组织和叶酸体外干预后Caski宫颈癌细胞中HPV16 E2及E6 mRNA水平,检测不同叶酸浓度对Caski和C33A细胞抑制情况。结果 CINⅠ组、CINⅡ/Ⅲ组和SCC组HPV16感染率分别与CI组宫颈组织HPV16感染率比较,差异具有统计学意义(P<0.05)。CINⅠ、CINⅡ/Ⅲ、SCC各组HPV16 E2和E6 mRNA水平与CI组比较差异均具有统计学意义(P<0.0001)。宫颈癌的严重程度与HPV16 E2和E6 mRNA水平均呈明显正相关性,与血清叶酸和红细胞叶酸含量均呈显著负相关性。叶酸浓度与Caski细胞和C33A细胞的相对抑制率及HPV16 E2和E6 mRNA水平呈明显负相关性。结论叶酸水平低、HPV16感染及HPV16 E2及E6 mRNA低表达均与宫颈癌变有关,补充叶酸明显抑制宫颈癌细胞的增殖,逆转HPV16 E2及E6高表达,提示叶酸水平及HPV16感染在宫颈癌变的过程中具有协同作用。Objective To investigate the relationship of level of folate,HPV16 infection,mRNA levels of HPV16 E2 and E6 and cervical carcinogenesis,and the synergistic effect of folate levels and HPV16 infection on development of cervical cancer.Methods 40 patients with cervical inflammation（ CI）,80 patients with cervical intraepithelial neoplasia（ CIN）（ 36 cases of CINⅠ,44 cases of CINⅡ / Ⅲ） and 48 patients with cervical squamous cell carcinoma（ SCC） were chosen for the study. The content of serum folate and red blood cell folate were detected with microbiological method. And the HPV16 infection and mRNA levels of HPV16 E2 and E6 in cervical cancer tissues and Ca Ski cervical cancer cells were tested using quantitative PCR. Meanwhile,the vitro effect of folic acid intervention on proliferation of HPV16-positive Ca Ski cervical cancer cells and HPV-negative C33 A cervical cancer cells. Results 1 HPV16 infection in CINⅠgroup,CINⅡ / Ⅲ group and SCC group showed statistically significant compared with that in CI group（ P〈0. 05）. 2 mRNA levels of HPV16 E2 and E6 in groups of CIN,CINⅡ / Ⅲ and SCC were statistically significant differences when compared with those in CI group（ P〈0. 0001）. The severity of the cancer showed a positive correlation with mRNA levels of HPV16 E2 and E6,but showed a negative correlation with content of serum folate and RBC folate. 3 The content of serum folate was negatively correlated with the relative inhibition rate of Caski and C33 A as well as mRNA levels of HPV16 E2 and E6. Conclusion The decreased folate levels and lower mRNA expression of HPV16 E2 and E6 mRNA as well as HPV16 infection are associated with lower development of cervical cancer. Adding folic acid could significantly inhibit the proliferation of cancer cells and reverse the high expression of HPV16 E2 and E6,implying the synergistic effect of folate levels and HPV16 infection on development of cervical cancer.

关 键 词：叶酸 HPV16 E2 E6 宫颈癌 

分 类 号：R737.33[医药卫生—肿瘤]