辛伐他汀对结直肠癌患者IL-6与IL-8血清表达及癌细胞分泌影响的研究

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Ca-co-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14 d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5μmol/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。

Effect of simvastatin on IL-6 and IL-8 responses of colorectal cancer and cancer cells

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 colorectal 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.