去甲二氢愈创木酸对恶性胶质瘤细胞基因组甲基化水平的影响及其意义

目的：探讨去甲二氢愈创木酸（NDGA）诱导人恶性胶质瘤细胞系SHG－44细胞分化过程中基因组甲基化状态改变及其意义。方法：合成甲基化敏感性AP－PCR引物，用AP－PCR方法检测SHG－44细胞基因组甲基化状态，观察NDGA诱导该细胞分化过程中甲基化水平的变化。结果：对照组基因组DNA经MspI酶解后AP－PCR扩增片段比HpaII酶解后的扩增片段小，几乎未见存留大片段，至少有3个片段与HpaII酶解片段不同。同一时相点HpaII酶解后扩增产物相比，NDGA处理后基因组DNA Msp I酶解后的扩增产物量较少、条带较多，且随时相点延长产物量逐渐增加，条带增多。结论：NDGA诱导人恶性胶质瘤细胞SHG－44细胞分化过程中基因组甲基化状态增高，推测基因组甲基化状态可能是NDGA诱导胶质瘤细胞分化的作用靶点之一。

Effects of nordihydroguaiaretic acid on genomic methylation pattern of malignant glioma cells and its significance

Objective　To investigate the genomic methylation pattern of a malignant glioma cell line in the process of differentiation induced by nordihydroguaiaretic acid (NDGA). Methods　Methylation-sensitive arbitrarily primed PCR was used to study the genomic methylation changes. Results　Fragments of genomic DNA of PCR products in control groups digested with MspⅠ were smaller than those with HpaⅡ. No large fragment could be identified and at least three fragments of different sizes were demonstrated in the control group. In NDGA treatment group, comparing MspⅠ digestion with HpaⅡ digestion, the amount of PCR products was smaller with more DNA bands. The amount of PCR products in NDGA treatment group was increased with more DNA bands compared with that in the control groups. Conclusion　The genomic methylation level in SHG-44 cells was increased by NDGA in the differentiation process of SHG-44 cells. It suggests that genomic methylation pattern may be one of the targets for glioma cell differentiation induced by NDGA.