端粒酶反义寡核苷酸及顺铂对恶性脑胶质瘤治疗的协同作用

The cooperative effect of telomerase antisense oligodeoxynucleotide with cisplatin on the inhibition of malignant glioma

目的观察端粒酶反义寡核苷酸(ODN)及顺铂对恶性脑胶质瘤治疗的协同作用。方法用15例Ⅲ、Ⅳ级端粒酶活性阳性表达的恶性脑胶质瘤制备单细胞悬液并原代培养,以5μmol／L端粒酶反义ODN抑制恶性胶质瘤细胞端粒酶活性后,用不同浓度顺铂处理细胞。流式细胞仪检测处理前后胶质瘤细胞PCNA、TUNEL阳性百分率变化情况。结果端粒酶反义ODN作用于恶性胶质瘤细胞72h后,TRAP法检测端粒酶活性转为阴性,此时0．3μg／mL顺铂即可对胶质瘤细胞有明显抑制增殖、促进凋亡作用。结论端粒酶反义ODN能抑制端粒酶活性,增加恶性胶质瘤细胞对顺铂的敏感性,与顺铂在治疗恶性脑胶质瘤细胞过程中有协同作用。

Objective To investigate the cooperative effect of telomerase antisense oligodeoxynucleotide（ODN） with cisplatin on the inhibition of malignant glioma. Methods In fifteen cases of Ⅲ and Ⅳ grade glioma specimens, whose telomerase expression were detected positively, the 5 μmol/L telomerase antisense oligodeoxynucleotide, was hatched with cultured cells of the gliomas and only cisplatin group was used as control. PCNA and TUNEL positive rates were detected by flow cytometer（FLM） at both the beginning and the end of the therapy. Results At 48 h anti-sense ODN inhibited telomerase activity,and telomerase activity was negative at 72 h. At that time, the malignant glioma cells in antisense oligodexynucleotide group were treated with 0.3 μg/ mL cisplatin, it was found that the cell proliferation significantly inhibited, the apoptosis was increased, and no notable effect was found in simple chemotherapy group. Conclusion Anti-sense telomerase ODN could inhibit telomerase activity of the malignant glioma cells,increase its sensitivity to chemotherapy. The telomerase antisense oligodeoxynucleotide and cisplatin playe the cooperative effect on the inhibition of malignant glioma.