缺氧诱导因子抑制剂YC-1对口腔鳞癌Glut1、VEGF表达的抑制效应

目的 探讨缺氧诱导因子抑制剂YC-1对口腔鳞癌(OSCC)中葡萄糖转运蛋白-1(Glut1)、血管内皮生长因子(VEGF)基因的调控作用。方法 (1)应用免疫组织化学法检测60例OSCC患者和12例癌旁正常组织中的缺氧诱导因子-1α(HIF-1α)、Glut1、VEGF的表达。(2)人舌癌Tca8113细胞在体外进行培养,将其分成缺氧组、常氧组。将浓度为0、10、100 μmmol/L的HIF-1α抑制剂YC-1分别加入二组后,通过RT-PCR技术检测OSCC细胞中HIF-1α、Glut1、VEGF mRNA的转录水平。结果 免疫组化发现:OSCC癌中HIF-1α、Glut1、VEGF的阳性表达明显多于正常组织,其中HIF-1α的阳性表达与Glut1的阳性表达、VEGF的阳性表达均呈正相关。RT-PCR结果表明,加入YC-1后,HIF-1α的表达在缺氧组和常氧组中均降低,差异有统计学意义(P＜0.05)。HIF-1α的表达在缺氧组随着YC-1浓度不同无剂量依从性,差异无统计学意义(P＞0.05)。在YC-1作用下,缺氧组和对照组Glut1、VEGF在人舌癌Tca8113细胞中的表达均显著(P＜0.05)降低,缺氧组内Glut1、VEGF的表达随着YC-1浓度增加有剂量依从性(P＜0.05)。结论 HIF-1α、Glut1、VEGF高表达于OSCC组织中。YC-1显著抑制人舌癌Tca8113细胞HIF-1α、Glut1、VEGF分子的表达;YC-1可能通过下调HIF-1α、Glut1、VEGF的表达来抑制OSCC的生长。

Inhibitory effect of YC-1 on induction of Glut1 and VEGF genes in Oral squamous cell carcinoma

Objective To study the function and mechanism of YC-1 on activity of Glut1 and VEGF genes in Oral squamous cell carcinoma.Methods (1) HIF-1α,Glut1 and VEGF proteins were detected by immunohistochemical methods in 60 cases of oral squamous cell carcinoma and 12 cases of normal tissue adjacent to tumor. (2) Human tongue squamous cancer cell line Tca8113 were incubated under hypoxic or normoxia conditions and were divided into the hypoxia group and the normoxic group. Different concentrations of YC-1 (0, 10, and 100 μmol/L) were added to both groups.RT-PCR was used to detect the HIF-1α,Glut1 and VEGF mRNA.Results The positive expression rate of HIF-1α,Glut1 and VEGF in OSCC was higher than that in normal tissue. Positive correlation was found between HIF-1α and Glut1,VEGF expression (P＜0.05).RT-PCR results showed that after the adding of YC-1,the expression of HIF-1α in both groups decreased,with statistical significant difference (P＜0.05).With different YC-1 concentration,the expression of HIF-1α in the hypoxia group had no dose dependence,with no statistical significant difference (P＞0.05).Glut1 and VEGF molecular expressions in human tongue squamous cancer cell line Tca8113 decreased significantly in different YC-1 concentrations (P＜0.05).The expressions of Glut1 and VEGF had dose dependence in the hypoxia group with the increase of YC-1 concentrations (P＜0.05).Conclusion The expression levels of HIF-1α,Glut1 and VEGF in oral squamous cell carcinoma are higher than those in the normal tissues.YC-1 inhibits HIF-1α,Glut1 and VEGF expressions in Tongue squamous cancer cell line Tca8113. YC-1 inhibits the growth of OSCC possibly through down-regulating the expressions of HIF-1α,Glut1 and VEGF.