FoxO3在复发胶质母细胞瘤中的表达及其对替莫唑胺耐药性的影响

目的：研究抑癌基因FoxO3在复发胶质母细胞瘤中的表达及其在胶质母细胞瘤替莫唑胺耐药中的潜在作用机制。方法：通过基因芯片分析、qPCR和Western blot检测FoxO3在原发和复发胶质母细胞瘤中的表达，并检测其在替莫唑胺耐药细胞株中的表达。通过FoxO3过表达芯片筛选其下游靶基因，并进一步探讨FoxO3在胶质母细胞瘤替莫唑胺耐药中的作用机制。结果：FoxO3 mRNA及蛋白的表达在复发胶质母细胞瘤组织及耐替莫唑胺细胞系中明显减低。过表达FoxO3可通过抑制跨损伤修复蛋白REV3L的表达来增加胶质母细胞瘤细胞对替莫唑胺的敏感性。结论：FoxO3在复发胶质母细胞瘤组织中表达减低。FoxO3表达减低与胶质母细胞瘤化疗耐药密切相关。FoxO3可能通过抑制REV3L基因表达增加胶质母细胞瘤细胞对替莫唑胺的化疗敏感性。

Preliminary study on the expression of FoxO3 in recurrent glioblastoma and its resistance to chemotherapy

Objective: To explore the expression level of tumor suppressor gene FoxO3 in the recurrent glioblastoma tissues and its potential function in temozolomide(TMZ) resistance. Methods: The expression level of FoxO3 mRNA and protein were detected and compared in primary and recurrent glioblastoma tissues via microarray, qPCT and Western blot. And then to explore the potential mechanism of FoxO3 mediated in TMZ resistance by screening its target using a microarray. Results: The expression level of FoxO3 mRNA and protein is decreased both in recurrent glioblastoma tissues and TMZ- resistance glioblastoma cell lines. Overexpression of FoxO3 could sensitize glioblastoma cells to TMZ via modulating the expression of REV3L. Conclusion: The expression level of FoxO3 is decreased in recurrent glioblastoma tissues, which might play a pivotal role in chemotherapy-resistance. Overexpression of FoxO3 could sensitize glioblastoma cells to TMZ via suppressing the expression of REV3L.