Autophagy in Combination Therapy of Temozolomide and Ifn-Γin C6-Induced Glioblastoma: Role of Non-Coding Rnas Publisher Pubmed



Bashiri H¹ ; Moazamjazi M² ; Karimzadeh MR³ ; Jafarinejadfarsangi S⁴ ; Moslemizadeh A⁵ ; Lotfian M⁶ ; Karam ZM⁷ ; Kheirandish R⁸ ; Farazi MM¹ Show Affiliations
Source: Immunotherapy Published:2023

Abstract

Aim: We predicted the modulation of autophagy and apoptosis in response to temozolomide (TMZ) and IFN-γbased on changes in the expression of non-coding RNAs in C6-induced glioblastoma (GBM). Materials & methods: Each rat received an intraperitoneal injection of TMZ (7.5 mg/kg) and/or IFN-γ(50,000 IU). Results: The reduced expression of H19 and colorectal neoplasia differentially expressed (CRNDE) was associated with a reduction in autophagy in response to TMZ, IFN-γand TMZ + IFN-γtherapy, whereas the decreased level of miR-29a (proapoptotic miRNA) was associated with an increase in apoptosis. Conclusion: It appears that H19 promotes switching from autophagy to apoptosis in response to combination therapy of TMZ and IFN-γthrough the miR-29a/autophagy-related protein 9A (ATG9A) pathway in C6-induced GBM. Plain language summary Temozolomide (TMZ) is a drug for people with brain cancer. It can make it hard for patients to learn and think, and it can also make the drug stop working, which lets the tumor keep growing. Researchers are looking for other drugs or things that can be taken with TMZ to stop this from happening. In this study, we used a protein called interferon (IFN), which helps fight cancer. We gave mice with brain cancer both TMZ and IFN, and saw that the tumor cells died and the tumor got smaller. We also looked at how IFN and TMZ changed the genetic material of the mouse brain, called RNA. But we need to test this on people to be sure it works. Tweetable abstract TMZ in combination with IFN-γswitched autophagy to apoptosis in C6-induced GBM in rats through H19/miR-29a/ATG9A axis. Graphical abstract