结肠癌细胞株和组织中EGFR、p-EGFR和p-IGFR-1β的表达及意义

Expression and Significance of EGFR,p-EGFR and p-IGFR-1β in Human Colorectal Cancer Cell Lines and Specimen Tissues

目的:研究EGFR、p-EGFR和p-IGFR-1β在结肠癌细胞株的表达及其与吉非替尼敏感性的关系,以及在肿瘤组织中的表达状况、相关性及其与临床病理参数的关系。方法:以western blot检测EGFR、p-EGFR和p-IGFR-1β在结肠癌细胞株和组织中的表达,以Quantity One软件测量各蛋白条带的灰度值。结果:EGFR、p-EGFR在Lovo细胞中表达量最高(P<0.05),EGFR在SW620细胞中的表达最低(P<0.05),在HCT116、HT29、LS174T和SW480细胞中的表达差异不显著。p-IGFR-1β在Lovo、HT29和SW480细胞中表达较弱,且在Lovo细胞中表达更弱,但在HCT116、LS174T和SW620细胞中的表达均较强(P<0.05)。结肠癌组织中EGFR表达率为55.6%(10/18),癌旁正常组织为37.5%(3/18),肿瘤组织中有表达增高的趋势;p-EGFR在结肠癌组织表达率为33.3%(6/18),较正常组织的5.6%(1/18)明显增高(P<0.05);p-IGFR-1β在结肠癌组织表达率为44.4%(8/18),较正常组织的11.1%(2/18)明显增高(P<0.05)。EGFR、p-EGFR和p-IGFR-1β相互之间的表达无明显相关性;EGFR、p-EGFR表达与各临床病理参数无明显相关;p-IGFR-1β在淋巴结转移患者中的表达显著增高(P<0.05),且在分期晚的患者中也可观察到这种趋势。结论:结合我们以往的研究结果,p-EGFR表达高伴p-IGFR-1β表达低提示结肠癌细胞对吉非替尼的敏感性好。p-EGFR和p-IGFR-1β在结肠癌组织中的表达较正常组织明显增高,且p-IGFR-1β表达高可能预示结肠癌患者有较高的转移风险。

Objective： To investigate relationships of expression levels of EGFR, p-EGFR and p-IGFR-1 β in colorectal cancer cell lines with their sensitivities to gefitinib, and assess relationships of the expression in specimen tissues with clinicopathological parameters of colorectal cancer patients. Methods： The levels of EGFR, p-EGFR and p-IGFR-1β expression were determined with western blot anal- ysis after gross protein was extracted. Band gray scale scan was performed to evaluate the relative value of protein expression. Results： EGFR or p-EGFR was expressed highest in Lovo cells, lowest in SW620 cells （P〈0.05）, and no differences among the other cell lines. p-IGFR-1β was undetectable or expressed at very low levels in the most and moderate gefitinib-sensitive cell lines （Lovo, HT29 and SW480） and was seemingly much lower in the most sensitive cell line （Lovo） than in the moderate ones （HT29 and SW480） and however, expressed at strikingly high levels in all resistant cell lines （HCT116, LSI74T and SW620）. 55.6%（10/18） cotorectal cancer specimens had higher levels of EGFR expression than 37.5%（3/18） did in normal tissue specimens from the same patients. 33.3%（6/18） tumor tissue had significant higher levels of p-EGFR than 5.6%（1/18） did in normal tissue （P〈0.05）. 44.4%（8/18） tumor tissue bad signifiearlt higher levels of p-IGFR-113 than 11.1%（2/18） did in normal tissue （P〈0.05）. The expression ofEGFR, p-EGFR and p-IGFR-1β had no correla- tion with each other. EGFR or p-EGFR expression did not show any association with the clinicopathological parameters, while p-IGFR-1β expression was significantly increased in patients with lymph node metastasis （P〈0.05）, and there was a same trend in pa- tients with advanced stage. Conclusion： With our previous study, it is suggested that the colorectal cancer cells were best sensitive to gefi- tinib, which expressed high p-EGFR and low p-IGFR-1β. The expression ofp-EGFR and p-IGFR-1β were both significantly increased in colorectal cancer tissue and were independent from each other, and increased p-IGFR-1 β expression may favor the metastasis of colorec- tal cancer.