APRIL在大肠癌组织中的表达及化疗药物对大肠癌SW480细胞APRIL表达的影响

Expression of APRIL in Colorectal Carcinoma Tissues and Effects of Chemotherapeutic Agents on APRIL Expression in Colorectal Carcinoma SW480 Cells

背景与目的:增殖诱导配体(a proliferation-inducing ligand,APRIL)是最近发现的肿瘤坏死因子家族新成员,有促进肿瘤生成和增殖的能力。本实验通过研究APRIL在大肠癌组织中的表达,并对比氟尿嘧啶和顺铂对大肠癌细胞株SW480表达APRIL水平的影响,探讨抗癌药对APRIL在大肠癌组织中表达的影响。方法:采用免疫组化法和荧光定量PCR检测56例大肠癌患者癌组织和配对癌旁相对正常组织及大肠癌细胞株SW480上APRIL的表达。将不同终浓度的氟尿嘧啶和顺铂加入培养中的SW480细胞,用荧光定量PCR检测加入药物后24h、48h和72hSW480细胞表达APRIL mRNA的水平。结果:大肠癌组织表达APRIL的阳性率为76.8%,mRNA水平为0.71±0.08,高于癌旁相对正常组织的16.1%和0.16±0.05(P<0.001)。SW480细胞上有明显的APRIL表达,加入不同浓度的氟尿嘧啶后,SW480细胞APRIL的mRNA水平逐渐升高,至72h表达最高,25、50、100、200μg/mL4个药物浓度作用72h后细胞APRIL mRNA水平分别为0.85±0.10、0.81±0.09、0.83±0.11和0.90±0.12,与空白对照(0.57±0.06)相比差异有统计学意义(P<0.001);而加入不同浓度的顺铂后,细胞APRILmRNA水平与空白对照相比差异无统计学意义(P>0.05),仅在10、20μg/mL浓度作用72h后细胞的APRIL mRNA水平(分别为0.44±0.05,0.40±0.07)低于空白对照(P<0.05)。结论:APRIL在大肠癌的进展过程中可能起到一定程度的促进作用;氟尿嘧啶可能具有对抗APRIL功能的潜在作用。

BACKGROUND ＆ OBJECTIVE： A proliferation-inducing ligand （APRIL）, a new member of the tumor necrosis factor （TNF） family, can stimulate tumor cell growth and proliferation both in vitro and in vivo. This research was to detect the expression of APRIL in colorectal carcinoma tissues, and to compare the effects of 5-fluorouracil （5-FU） and cisplatin （DDP） on the expression of APRIL in colorectal carcinoma SW480 cells. METHODS： The protein and mRNA levels of APRIL in 56 specimens of human colorectal carcinoma and para-tumor tissues and in SW480 cells were determined by immunohistochemistry and real-time fluorescence quantitative reverse transcription-polymerase chain reaction （FQ-RT-PCR）. SW480 cells were treated with 5-FU and DDP at various concentrations for 24 h, 48 h and 72 h. The changes of APRIL mRNA level were analyzed by FQ-RT-PCR. RESULTS.. Both positive rate and mRNA level of APRIL were significantly higher in colorectal carcinoma tissues than in para-tumor tissues （76.8% vs. 16.1%, 0.16±0.05 vs. 0.71 ±0.08, both P〈0.001）. The expression of APRIL was strong in SW480 cells. When treated with different concentrations of 5-FU, the mRNA level of APRIL in SW480 cells raised gradually and reached the highest levels at 72 h after treatment （0.85±0.10, 0.81±0.09, 0.83±0.11, and 0.90±0.12 at the concentrations of 25, 50, 100 and 200 iJg/mL, respectively）, which were significantly higher than those in blank control group （P〈0.001）. When treated with different concentrations of DDP, the mRNA level of APRIL in SW480 cells did not increase when compared with that in control group （P〉0.05）. After 72-hour treatment, the mRNA level of APRIL in SW480 cells was significantly lower in 10 μg/mL and 20 iJg/mL DDP groups than in blank control group （0.44±0.05 and 0.40±0.07 vs. 0.57±0.06, P〈 0.05）. CONCLUSIONS. APRIL may promote the development of colorectal carcinoma. When chemotherapy is conducted to treat colorectal carcinoma, especially when 5-FU is included in the regimen, anti-APRIL therapy might be an important assistant treatment to counter the impact of APRIL caused by antitumor drugs.