Combination of B7H6-siRNA and temozolomide synergistically reduces stemness and migration properties of glioblastoma cancer cells

Exp Cell Res. 2023 Aug 1;429(1):113667. doi: 10.1016/j.yexcr.2023.113667. Epub 2023 May 27.

Abstract

Glioblastoma multiforme (GBM) is among the malignant brain tumors of the central nervous system (CNS). The survival of this disease is about 14 months after diagnosis. To date, temozolomide is known as first-line therapy for glioma. Drug resistance and severe side effects against this drug are important obstacles to the effective treatment of this cancer. Small interfering RNA (siRNA) can adjust the expression of several genes and is used as a new method of gene therapy. Recent studies have shown that siRNAs can increase the sensitivity of cancer cells to chemotherapy drugs. This study aimed to understand the potential role and molecular mechanism of the combination therapy of B7H6-siRNA and temozolomide in glioblastoma cancer. U87 cells were treated with B7H6-siRNA and temozolomide, separately and in combination. Cell viability, stemness, cell migration, and apoptosis were measured. The results of this work presented the synergistic effect of B7H6-siRNA and temozolomide in inhibiting the cancerous features of the U87 cell line. Down-regulating B7H6-siRNA expression inhibited the cell viability of U87 glioblastoma cancer cells and increased their sensitivity to temozolomide. In addition, a noteworthy decrease in cell migration ability and stemness, an increase in apoptosis were observed in the combined groups compared to B7H6-siRNA and temozolomide individually. According to the results, a combination of B7H6-siRNA and temozolomide can be a promising strategy in glioblastoma cancer therapy.

Keywords: B7H6-siRNA; Cancer stem cells; Combination therapy; Glioblastoma; Temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Apoptosis
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Glioblastoma* / drug therapy
  • Glioblastoma* / genetics
  • Glioblastoma* / pathology
  • Humans
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use

Substances

  • Temozolomide
  • RNA, Small Interfering
  • Antineoplastic Agents, Alkylating