HPV感染对宫颈COX-2表达及血PGE_2表达水平的影响
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摘要
目的探讨人乳头状瘤病毒(HPV)感染对宫颈组织环氧合酶-2(COX-2)及血前列腺素E_2(PGE_2)表达水平的影响及其相互关系。方法采用杂交捕获Ⅱ代技术检测HPV,实时荧光定量聚合酶链反应(qRT-PCR)检测宫颈组织COX-2 mRNA表达情况,酶联免疫吸附试验(ELISA)检测血PGE_2含量。结果 HPV DNA载量及COX-2表达均与宫颈病变程度呈正相关(P<0.05)。与HPV阴性患者比较,HPV阳性患者血PGE_2含量升高(P<0.05),随着HPV病毒载量升高,血PGE_2含量随之升高,呈正相关(r_s=0.257,P=0.003)。宫颈癌患者COX-2表达与PGE_2含量呈正相关(r_s=0.684,P=0.000)。结论在HPV感染的宫颈癌患者中,宫颈组织COX-2高表达,血PGE_2含量升高,其相互作用可能在宫颈癌的增殖、凋亡耐受、侵袭及转移过程中占据重要位置,为临床治疗宫颈癌提供了新的思路。
Objective To investigate the effect of by human papilloma virus(HPV)infection on cyclooxygenase cyclooxygenase 2(COX-2)and prostaglandin E_2(PGE_2)expression.Methods Hybrid capture 2testing method was applied for HPV detection.Real-time PCR and ELISA was performed for detection of COX-2 in cervical tissue and serum PGE_2.Results Load of HPV DNA and expression of COX-2 were positively correlated with the degree of cervical lesions(P<0.05).Compared with HPV negative patients,the serum levels of PGE_2 was increased significantly along with increase of HPV DNA load(P<0.05).The expression of COX-2 was positively correlated with the content of PGE_2 in patients with cervical cancer(r=0.684,P=0.000).Conclusions High expression of COX-2 and PGE_2 may be involved in development and progression of cervical cancer,which could provide a novel point for drug developement.
Objective To investigate the effect of by human papilloma virus(HPV)infection on cyclooxygenase cyclooxygenase 2(COX-2)and prostaglandin E_2(PGE_2)expression.Methods Hybrid capture 2testing method was applied for HPV detection.Real-time PCR and ELISA was performed for detection of COX-2 in cervical tissue and serum PGE_2.Results Load of HPV DNA and expression of COX-2 were positively correlated with the degree of cervical lesions(P<0.05).Compared with HPV negative patients,the serum levels of PGE_2 was increased significantly along with increase of HPV DNA load(P<0.05).The expression of COX-2 was positively correlated with the content of PGE_2 in patients with cervical cancer(r=0.684,P=0.000).Conclusions High expression of COX-2 and PGE_2 may be involved in development and progression of cervical cancer,which could provide a novel point for drug developement.
引文
[1]ATTFIELD M D,SCHLEIFF P L,LUBIN J H,et al.The diesel exhaust in miners study:a cohort mortality study with emphasis on lung cancer[J].J Natl Cancer Inst,2012,104(11):869-883.
[2]TAKEUCHI O,AKIRA S.Pattern recognition receptors and inflammation[J].Cell,2010,140(6):805-820.
[3]ENGELS E A,WU X,GU J,et al.Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer[J].Cancer Res,2007,67(13):6520-6527.
[4]PLUMMER M,MARTEL C D,VIGNAT J,et al.Global burden of cancers attributable to infections in 2012:a synthetic analysis[J].Lancet Global Health,2016,4(9):e609.
[5]乔友林,赵宇倩.宫颈癌的流行病学现状和预防[J].中华妇幼临床医学杂志:电子版,2015,11(2):1-6.
[6]刘秀梅.不同程度宫颈病变与高危型人乳头瘤病毒病毒载量的相关性分析[J].中国妇幼保健,2015,30(20):3390-3392.
[7]马晓星,李亚里,胡凌云,等.HR-HPV载量与宫颈病变的相关性分析[J].解放军医学杂志,2012,37(5):477-481.
[8]KANG W D,KIM C H,CHO M K,et al.HPV-18 is a poor prognostic factor,unlike the HPV viral load,in patients with stage IB-II A cervical cancer undergoing radical hysterectomy[J].Gynecologic Oncology,2011,121(3):546-550.
[9]KIM J,VAISH V,FENG M,et al.Transgenic expression of cyclooxygenase-2(COX2)causes premature aging phenotypes in mice[J].Aging,2016,8(10):2392-2405.
[10]RANJBAR M M,ASSADOLAHI V,YAZDANI M,et al.Virtual Dual inhibition of COX-2/5-LOX enzymes based on binding properties of alpha-amyrins,the anti-inflammatory compound as a promising anti-cancer drug[J].EXCLI Journal,2016(15):238-245.
[11]ATHAVALE R,CLOONEY K,O'HAGAN J,et al.COX-1 and COX-2 expression in stage I and II invasive cervical carcinoma:relationship to disease relapse and long-term survival[J].International Journal of Gynecological Cancer,2006,16(3):1303-1308.
[12]ZHOU W Q,SHENG Q Y,SHENG Y H,et al.Expressions of survivin,P16(INK4a),COX-2,and Ki-67 in cervical cancer progression reveal the potential clinical application[J].European Journal of Gynaecological Oncology,2015,36(1):62.
[13]WU L,TAO G,CHEN Y,et al.The influence of COX-2 inhibitor on the expression of HPV18-E6 and COX-2 in Hela cells[J].Journal of Modern Oncology,2016,24(24):3897-3900.
[14]SUBBARAMAIAH K,ALTORKI N,CHUNG W J,et al.Inhibition of cyclooxygenase-2 gene expression by p53[J].The Journal of Biological Chemistry,1999,274(16):10911-10915.
[15]GHARGHABI M,REZAEI F.Celecoxib treatment alters p53 and MDM2 expression via COX-2 crosstalk in A549 cells[J].Iranian Journal of Pharmaceutical Research(IJPR),2016,15(2):483-489.
[16]邹余粮,张鹏花,苟文丽,等.CIN和宫颈癌患者手术前后血清及病变组织中PGE2水平变化及意义[J].医学争鸣,2009(19):2008-2010.
[17]SALES K J,KATZ A A,HOWARD B,et al.Cyclooxygenase-1is up-regulated in cervical carcinomas:autocrine/paracrine regulation of Cyclooxygenase-2,prostaglandin E receptors,and angiogenic factors by cyclooxygenase-1[J].Cancer Research,2002,62(2):424.
[18]DEVA R,SCZEPANSKI M,SAHA S,et al.Calbicans activates cyclooxygenase but not its product prostaglandin E2 in HPV16-stabilized cells[J].European Journal of Obstetrics Gynecology&Reproductive Biology,2010,152(2):205.
[19]JUNGMIN O H,JUHNN Y S.Human papillomavirus 16 E5protein induces expression of prostaglandin E2 receptor EP4subtype through cyclooxygenase-2 dependent pathway in cervical cancer cells[J].Cancer Research,2008(5):68.
[20]EINSTEIN M H,SMITH K M,DAVIS T E,et al.Clinical evaluation of the cartridge-based genexpert human papillomavirus assay in women referred for colposcopy[J].Journal of Clinical Microbiology,2014,52(6):2089-2095.
[21]RABAAN A A,TAYLOR D R,DAWAMNEH M F,et al.Comparison of Xpert(?)HPV and Hybrid Capture(?)2 DNAtest?for detection of high-risk HPV infection in cervical atypical squamous cells of undetermined significance[J].Journal of Infection&Public Health,2017,10(2):219-223.
[2]TAKEUCHI O,AKIRA S.Pattern recognition receptors and inflammation[J].Cell,2010,140(6):805-820.
[3]ENGELS E A,WU X,GU J,et al.Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer[J].Cancer Res,2007,67(13):6520-6527.
[4]PLUMMER M,MARTEL C D,VIGNAT J,et al.Global burden of cancers attributable to infections in 2012:a synthetic analysis[J].Lancet Global Health,2016,4(9):e609.
[5]乔友林,赵宇倩.宫颈癌的流行病学现状和预防[J].中华妇幼临床医学杂志:电子版,2015,11(2):1-6.
[6]刘秀梅.不同程度宫颈病变与高危型人乳头瘤病毒病毒载量的相关性分析[J].中国妇幼保健,2015,30(20):3390-3392.
[7]马晓星,李亚里,胡凌云,等.HR-HPV载量与宫颈病变的相关性分析[J].解放军医学杂志,2012,37(5):477-481.
[8]KANG W D,KIM C H,CHO M K,et al.HPV-18 is a poor prognostic factor,unlike the HPV viral load,in patients with stage IB-II A cervical cancer undergoing radical hysterectomy[J].Gynecologic Oncology,2011,121(3):546-550.
[9]KIM J,VAISH V,FENG M,et al.Transgenic expression of cyclooxygenase-2(COX2)causes premature aging phenotypes in mice[J].Aging,2016,8(10):2392-2405.
[10]RANJBAR M M,ASSADOLAHI V,YAZDANI M,et al.Virtual Dual inhibition of COX-2/5-LOX enzymes based on binding properties of alpha-amyrins,the anti-inflammatory compound as a promising anti-cancer drug[J].EXCLI Journal,2016(15):238-245.
[11]ATHAVALE R,CLOONEY K,O'HAGAN J,et al.COX-1 and COX-2 expression in stage I and II invasive cervical carcinoma:relationship to disease relapse and long-term survival[J].International Journal of Gynecological Cancer,2006,16(3):1303-1308.
[12]ZHOU W Q,SHENG Q Y,SHENG Y H,et al.Expressions of survivin,P16(INK4a),COX-2,and Ki-67 in cervical cancer progression reveal the potential clinical application[J].European Journal of Gynaecological Oncology,2015,36(1):62.
[13]WU L,TAO G,CHEN Y,et al.The influence of COX-2 inhibitor on the expression of HPV18-E6 and COX-2 in Hela cells[J].Journal of Modern Oncology,2016,24(24):3897-3900.
[14]SUBBARAMAIAH K,ALTORKI N,CHUNG W J,et al.Inhibition of cyclooxygenase-2 gene expression by p53[J].The Journal of Biological Chemistry,1999,274(16):10911-10915.
[15]GHARGHABI M,REZAEI F.Celecoxib treatment alters p53 and MDM2 expression via COX-2 crosstalk in A549 cells[J].Iranian Journal of Pharmaceutical Research(IJPR),2016,15(2):483-489.
[16]邹余粮,张鹏花,苟文丽,等.CIN和宫颈癌患者手术前后血清及病变组织中PGE2水平变化及意义[J].医学争鸣,2009(19):2008-2010.
[17]SALES K J,KATZ A A,HOWARD B,et al.Cyclooxygenase-1is up-regulated in cervical carcinomas:autocrine/paracrine regulation of Cyclooxygenase-2,prostaglandin E receptors,and angiogenic factors by cyclooxygenase-1[J].Cancer Research,2002,62(2):424.
[18]DEVA R,SCZEPANSKI M,SAHA S,et al.Calbicans activates cyclooxygenase but not its product prostaglandin E2 in HPV16-stabilized cells[J].European Journal of Obstetrics Gynecology&Reproductive Biology,2010,152(2):205.
[19]JUNGMIN O H,JUHNN Y S.Human papillomavirus 16 E5protein induces expression of prostaglandin E2 receptor EP4subtype through cyclooxygenase-2 dependent pathway in cervical cancer cells[J].Cancer Research,2008(5):68.
[20]EINSTEIN M H,SMITH K M,DAVIS T E,et al.Clinical evaluation of the cartridge-based genexpert human papillomavirus assay in women referred for colposcopy[J].Journal of Clinical Microbiology,2014,52(6):2089-2095.
[21]RABAAN A A,TAYLOR D R,DAWAMNEH M F,et al.Comparison of Xpert(?)HPV and Hybrid Capture(?)2 DNAtest?for detection of high-risk HPV infection in cervical atypical squamous cells of undetermined significance[J].Journal of Infection&Public Health,2017,10(2):219-223.