TP、TS及其调变剂INF-γ增强氟尿嘧啶类药物抗大肠癌活性的研究

目的探讨胸苷磷酸化酶(thymidine phosphorylase,TP)及胸苷酸合酶(thymidylate synthase,TS)在正常大肠组织及大肠癌组织中的表达情况及γ-干扰素(interferon-γ,INF-γ)对其增强氟尿嘧啶(5-flurouracil,5-FU)抗癌活性的影响。方法收集本院术后接受5-FU化疗方案的48例大肠癌病理标本,另选取此48例患者的癌旁组织作为对照样本,应用免疫组化法测定大肠癌组织及癌旁组织中TP、TS表达水平,并分析INF-γ对其生长率及TPmRNA及TSmRNA转录的影响。结果与癌旁组织相比,大肠癌组织TP、TS阳性表达率显著提高,差异有统计学(P0.05)。男性大肠癌患者TS阳性表达率较女性高,低分化腺癌患者TS阳性表达率更高,淋巴结转移及TNM分期越高的患者其TS、TP阳性表达率越高。未经INF-γ诱导的大肠癌组织其TP、TS表达水平较弱,而经INF-γ诱导后大肠癌组织中TPmRNA及TSmRNA转录水平显著增强。结论大肠癌组织中TS、TP表达水平可能可作为患者对化疗药物敏感性的评价标准。通过INF-γ预处理可诱导大肠癌组织中TS、TP表达,从而增强化疗药物抗肿瘤的效果。

The Study of TP,TS and the Modulation Agent INF-V in the Fluoropyrimidine Activity for Colorectal Cancer

Objective To investigate the expression of thymidine phosphorylase （TP） and thymidylate synthase （TS） in colorectal cancer and the effects of the modulation agent interferon--γ （INF-γ） in the use of fluorouracil （5-FU）. Methods The expression levels of TP, TS were analyzed in colorectal cancer tissue （48 cases） and normal tissue （48 cases） by immunohistochemical methods. The inhibition ratio of the cultured ceils was analyzed with different concentration of INF-γ or without INF-γ Results The expression of TP and TS were significantly increased in colorectal cancer tissue comparing with the normal colon tissue （P 〈 0.05）. The expression of TP and TS was significantly related with the gender, differentiation, lymph node metastasis and TNM staging of patients. The TP and TS expression was weak without the induction of INF-γ, and the expression of TPmRNA and TSmRNA significantly increased when the INF-γ was added. Conclusion TS, TP expression levels may be used as 5-FU sensitivity evaluation criteria in colorectal carcinoma patients. And the pretreatment by INF-γ can induce the TS and TP expression in colorectal cancer tissues, thereby enhancing the anti-tumor effects of 5-FU.