Autophagy in combination therapy of temozolomide and IFN-γ in C6-induced glioblastoma: role of non-coding RNAs

Immunotherapy. 2023 Oct;15(14):1157-1169. doi: 10.2217/imt-2022-0212. Epub 2023 Aug 16.

Abstract

Aim: We predicted the modulation of autophagy and apoptosis in response to temozolomide (TMZ) and IFN-γ based 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-γ and TMZ + IFN-γ therapy, 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-γ through the miR-29a/autophagy-related protein 9A (ATG9A) pathway in C6-induced GBM.

Keywords: C6-induced GBM; CRNDE; H19; IFN-γ; glioblastoma; miR-29a; non-coding RNA; temozolomide.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Apoptosis
  • Autophagy
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics
  • Glioblastoma* / drug therapy
  • MicroRNAs* / genetics
  • Rats
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use

Substances

  • Temozolomide
  • MicroRNAs
  • Antineoplastic Agents, Alkylating