Cordycepin improves sensitivity to temozolomide in glioblastoma cells by down-regulating MYC

Shi-Xing Zheng1, Jing Chen2, Bing-Bo Zhuang1

  • 1Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China.

Abstract

Insights

This study shows cordycepin and temozolomide combination effectively inhibits glioblastoma growth and migration. The combination targets key cancer pathways, offering a potential new treatment for this aggressive brain tumor.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Glioblastoma is an aggressive brain tumor with limited treatment options and poor prognosis.
  • Current treatments for glioblastoma often face challenges with efficacy and resistance.

Purpose of the Study:

  • To investigate the synergistic effects of cordycepin combined with temozolomide on glioblastoma.
  • To elucidate the molecular mechanisms underlying the anti-cancer activity of this drug combination using network pharmacology and biological validation.

Main Methods:

  • Network pharmacology was employed to identify potential drug targets and pathways.
  • In vitro studies using LN-229 glioblastoma cells were conducted to assess cell growth, proliferation, migration, and invasion.
  • Gene and protein expression levels of key molecules involved in cancer pathways were analyzed.

Main Results:

  • The combination of cordycepin and temozolomide significantly inhibited glioblastoma cell growth, proliferation, migration, and invasion.
  • The drug combination suppressed epithelial-mesenchymal transition (EMT) by modulating E-cadherin, N-cadherin, Zeb1, and Twist1 expression.
  • Network pharmacology identified 36 common targets and highlighted pathways such as "MicroRNA in cancer" and "PI3K-AKT signaling pathway"; key gene expression changes included down-regulation of MYC and up-regulation of PDCD4.

Conclusions:

  • Cordycepin and temozolomide combination demonstrates significant anti-glioblastoma activity.
  • The mechanism involves down-regulating MYC via specific cancer-related pathways, subsequently affecting cell proliferation, migration, and apoptosis.
  • This combination therapy presents a promising strategy for glioblastoma treatment.

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