宫颈癌细胞凋亡逃逸与肿瘤坏死因子相关凋亡诱导配体及其受体的表达

Apoptosis escape of cervical cancer cells and the expressions of TRAIL and TRAIL receptor

目的选取正常宫颈组织、早期宫颈鳞癌组织、复发宫颈鳞癌组织采用免疫组化法(IHC),蛋白质印迹法(Western-blot,WB)检测肿瘤坏死因子相关凋亡诱导配体(TRAIL)及受体(TRAILR)的蛋白质表达量变化及表达部位,以探讨TRAIL/TRAILR系统在宫颈癌细胞凋亡中的作用。方法选择正常宫颈组织(Control组)、早期宫颈鳞癌组织(SCC组)、复发宫颈鳞癌组织(Recurret组)各30例,选取组织分为2份:分别进IHC、WB检测TRAIL及TRAILR蛋白质表达量的变化,并通过IHC确定其表达部位,数据通过SPSS软件进行统计学分析。结果 IHC及WB检测TRAIL及TRAILR蛋白质表达量数据分析:1TRAIL:3组中差异无统计学意义(P>0.05);宫颈癌细胞死亡受体(DR4,DR5):SCC组较Control组明显减少,差异有统计学意义(P<0.01),Recurrent组较Control组、SCC组明显增加,差异有统计学意义(P<0.01);诱骗受体(DcR1,DcR2):SCC组与Control组差异无统计学意义(P>0.05),Recurrent组较Control组、SCC组明显增加,差异有统计学意义(P<0.01);骨保护素(OPG):SCC组与Control组差异无统计学意义(P>0.05),Recurrent组较Control组、SCC组明显减少,差异有统计学意义(P<0.01)。2TRAIL及TRAILR IHC阳性表达主要定位于宫颈腺上皮细胞、血管平滑肌及内皮细胞的细胞膜和胞质等部位。结论 1TRAIL在宫颈炎症、早期癌变及复发的过程中的表达无显著性变化;2TRAILR在不同阶段发生了相应的变化;3在宫颈癌的早期阶段,宫颈癌细胞死亡受体DR4,DR5表达明显减少,诱骗受体无显著变化,宫颈癌细胞凋亡过程中得以免疫耐受与被保护,引起宫颈癌细胞的凋亡逃逸,与宫颈癌的发生、发展可能有关;在宫颈癌的复发阶段,宫颈癌细胞死亡受体DR4,DR5,诱骗受体DcR1,DcR2的表达均明显增加,OPG的表达显著减少,TRAIL/TRAILR系统显著失衡,宫颈癌细胞生长迅速,易发生转移。宫颈癌细胞凋亡逃逸与死亡受体、诱骗受体的表达差异,为TRAIL应用到临床治疗宫颈癌提供可能的实验依据。4OPG与宫颈癌细胞的凋亡逃逸是否有关尚需进一步研究。

Objective To detect the changes of expression levels and locations of tumor necrosis factor related apoptosis inducing lig- and （TRAIL） and its receptor （TRAILR） in normal cervix, early cervical squamous carcinoma, and recurrent cervical squamous carcinoma- by immunohistochemistry （IHC） and Western blot （WB）, explore TRAIL/TRAILR system in apoptosis of cervical cancer cells. Methods Thirty normal cervical tissues （control group）, and thirty early cervical squamous carcinoma tissues （SCC group）, and thirty re- current cervical squamous carcinoma tissues （recurret group） were selected; the tissues in each group were divided into two pieces for IHC and WB detection respectively to determine TRAIL/TRAILR protein expression levels, and the expression was located by IHC. SPSS software was used to analyze the data. Results There was no statistically significant difference in TRAIL expression level among the three groups （P 〉0. 05 ） ; the expression levels of death receptors （ DR4, DR5 ） in SCC group were statistically significantly lower than those in control group （ P〈0. 01 ）, the expression levels of death receptors （ DR4, DR5 ） in recurrent group were statistically significantly higher than those in con- trol group and SCC group （ P〈0. 01 ） ; there was no statistically significant difference in the expression levels of decoy receptors （ DcR1 and DcR2） between SCC group and control group （P〉0.05） , the expression levels of decoy receptors （DcR1 and DcR2） in recurrent group were statistically significantly higher than those in control group and SCC group （ P〈0. O1 ） ; there was no statistically significant difference in the expression level of osteoprotegerin （OPG） between SCC group and control group （P〉0. 05 ）, and the expression level of OPG in recur- rent group was statistically significantly lower than those in control group and SCC group （ P〈0.01 ） . IHC showed that TRAIL and TRAILR positive expressions mainly located in cell membrane and cytoplasm of cervical glandular epithelial cells, vascular smooth muscle cells, and endothelial cells. Conclusion TRAIL expression has no significant change in the process of cervical inflammation, early cervical cancer, and relapse; TRAILR has corresponding changes in different stages; during the early stage of cervical cancer, cervical cancer cell death re- ceptors （ DR4, DR5 ） expression levels significantly decrease, but the decoy receptors expression levels do no change significantly, which fa- cilitates cervical cancer for immune tolerance and protection in the process of cell apoptosis, thus it causes cervical cancer cell apoptosis es- cape and may be related to tumorigenesis and development of cervical cancer; during prolapse stage of cervical cancer, cervical cancer cells significantly express high levels of death receptors （ DR4, DR5 ） and decoy receptors （ DcR1, DcR2） and low level of OPG, significant im- balance of TRAIL/TRAILR system makes rapid growth and easy metastasis of cervical cancer cells. Apoptosis escape of cervical cancer cells and differentiated expression of death receptors and decoy receptors provide possible experimental basis for clinical application of TRAIL for treatment of cervical cancer. The correlation between OPG and apoptosis escape of cervical cancer cells still requires further studies.