中文摘要：

目的通过诱导非典型蛋白激酶C（aPKC）基因沉默增加胶质瘤干细胞对化疗药物的敏感性，为根治胶质瘤干细胞提供理论支持。方法流式细胞术分离大鼠c6胶质母细胞瘤侧群细胞，RNA干扰（RNAi）技术沉默c6侧群细胞aPKC表达，MTT和锥虫蓝实验检测单纯疱疹病毒-胸苷激酶（HSV-tk）／更昔洛韦（GCV）对c6侧群细胞的杀伤效果；建立裸鼠皮下胶质瘤模型，测量肿瘤体积，肿瘤组织块称重，原位凋亡法检测细胞凋亡。结果c6侧群细胞aPKC基因被有效沉默后，可显著增加其对HSV-tk／GCV药物的敏感性，表现为细胞凋亡和死亡数明显增加（P〈0．05）；体内实验显示肿瘤体积和重量较对照组明显减小（P〈0．05），细胞凋亡明显增加（P〈0．05）。结论通过诱导aPKC基因沉默可进一步增加胶质瘤干细胞对化疗药物HSV-tk／GCV的敏感性，为胶质瘤干细胞的基因治疗提供了新的方法选择。

英文摘要：

Objectives To increase the sensitivity of glioma stem cells to chemotherapeutic drugs by inducing atypical protein kinase C （aPKC） gene silence and to provide theoretical support for radical cure of glioma stem cells. Methods The side population cells in rat C6 glioblastonla were isolated by a flow cytometry. The expression of aPKC in C6 side population cells was silenced by RNA interference （RNAi） technology. MTI＂ and trypan blue assay were used to detect the killing effect of herpes simplex virus-thymidine kinase （HSV-tk）/ ganciclovir （GCV） on C6 side population cells. A subcutaneous glioma model in nude rats was induced. The volume and weight of glioma were measured. In situ apoptosis assay was used to detect cell apoptosis. Results After the aPKC genes in C6 side population cells being effectively silenced, they could significantly increase their sensitivity to HSV-tk/GCV drugs. They showed apoptosis and the number of death increased significantly （P 〈 0. 05 ）. The in vivo experiment showed that the volume and weight of glioma decreased significantly compared with the control group （ P 〈 0. 05 ）. The cell apoptosis increased significantly （ P 〈 0. 05 ）. Conclusion By inducing aPKC gene silencing, it may further increase the glioma stem cells to the sensitivity of chemotherapy drug HSV-tk/GCV and provide a new s election method for gene therapy of glioma stem cells.