Abstract
Background: The radical cure of Glioblastoma multiforme (GBM) is a troublesome medical problem, owing to its resistance to temozolomide chemotherapy and very poor surgical results or high relapse rate. Resistance to temozolomide emerges from numerous signalling pathways that are altered in GBM, especially the hedgehog signalling pathway. Hence, further research is urgent needed to identify more effective treatment modalities. Methods: We evaluated the effect of ATO on viability, cell proliferation, colony formation production. Flow cytometer assesses the degree of apoptosis, and Western blot analysis the expression of hedgehog signalling pathway proteins(Gli1, Gli2 and SMO). Moreover, use database(CGGA and TCGA) to inquire the relationship between Arrb1 expression level and miR-326 expression level in different levels of gliomas. Finally, The methylation sequencing level of CpG in Arrb1 gene with the survival period of nude mice gives a good explanation to the results of the Immunohistochemica.Results: Flow cytometer showed that the ATO caused apoptosis increased in a dose-dependent manner. Western blot analysis revealed the low expression of Gli1, Gli2 and SMO as well as the mRNA levels(included FOXM1). Arrb1 expression level was positively related with miR-326 expression level in different levels of gliomas from databases(CGGA and TCGA). Immunohistochemical analysis showed that ATO downregulated the expression of SMO, GLI1and Arrb1. The methylation level of CpG in Arrb1 gene was significantly reduced and the survival period of nude mice was prolonged by ATO. Conclusion: Our results showed that the cytotoxicity of ATO could be regulated by the SMO via Hh signalling pathway as well as miR-326, presenting a promising potential therapy for patients with GBM.