目的:研究辛伐他汀对结直肠癌患者IL-6及IL-8血清表达和癌细胞分泌的影响,初步探讨辛伐他汀在结直肠癌中的治疗机制.方法:应用ELISA检测结直肠癌患者与健康对照者血清中IL-6及IL-8水平,应用RT-PCR比较IL-6与IL-8在结直肠癌及癌旁组织的表达情况；应用ELISA检测结直肠癌患者辛伐他汀治疗后血清IL-6与IL-8的变化规律.应用ELISA检测辛伐他汀干预后结直肠癌细胞株(HT-29与Caco-2)上清中IL-6与IL-8变化.结果:结直肠癌患者血清IL-6与IL-8水平显著高于健康对照者(P＜0.05).IL-8 mRNA表达水平在癌组织明显高于癌旁组织(P＜0.05)；而IL-6 mRNA在癌组织与癌旁组织表达差异无统计学意义(P＞0.05).结肠癌患者应用辛伐他汀(80 mg/d)治疗14d后,血清IL-6水平显著降低(P＜0.05),而IL-8无明显变化(P＞0.05).应用浓度达到5 μmol/L以上辛伐他汀干预结直肠癌细胞株HT-29与Caco-2后,其IL-6及IL-8分泌明显下降(P＜0.05).结论:辛伐他汀可以降低结直肠癌患者血清IL-6的水平,并可以抑制结直肠癌细胞IL-8与IL-6分泌.%Objective: To explore the role of simvastatin in the treatment of colorectal cancer (CRC). Methods: Measure the serum levels of both IL-6 and IL-8 in CRC patients than in healthy volunteers with ELSA; compare the expression of IL-8 and IL-6 in tissue samples of tumor and adjacent normal colon mucosa obtained from patients with advanced(CRC) with RT-PCR; Measure the serum levels of both IL-6 and IL-8 in CRC patients after treatment with simvastatin(80 mg/day for 14 days)and in supernatant of coiorectal cancer-derived cell lines(HT-29 and Caco-2) treated with simvastatin. Results: The mean values of serum levels of both IL-6 and IL-8 were significantly higher in CRC patients than in healthy volunteers(P<0.05), The analysis of mRNAs expression for these proinflammatory cytokines determined by RT-PCR showed a higher level of IL-8-Mrna in tumor tissue than in normal mucosa(P< 0.05), while IL-6 was similarly expressed in tumor and normal tissue(P>0.05). Treatment of CRC with simvastatin(80 mg/day for 14 days) led to a significant decrease of serum IL-6(P< 0.05), while the IL-8 level was less affected(P> 0.05). The in vitro experiments on colorectal cancer-derived cell lines(HT-29 and Caco-2) demonstrated that application of simvastatin decreased generation of both IL-6 and IL-8(P < 0.05). Conclusion: Simvastatin therapy results in a decrease in serum level of IL-6 in CRC, and simvastatin inhibits release of IL-8 and IL-6 from colorectal cell lines.
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