Inducing atypical protein kinase C gene silence to increase the sensitivity of glioma stem cells to chemotherapeutic drugs

Abstract

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 glioblastoma were isolated by a flow cytometry. The expression of aPKC in C6 side population cells was silenced by RNA interference (RNAi) technology. MTT 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. Key words: Glioma; Neoplastic stem cells; Protein kinase C; RNA interference; Genes, transgenic, suicide