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Relationship between Hedgehog Signaling Pathway and Drug Resistance of Poorly Differentiated Gliomas

S A Cherepanov1,2, N F Grinenko3, O M Antonova3

  • 1N. I. Pirogov National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia. cherep-rsmu@yandex.ru.

Bulletin of Experimental Biology and Medicine
|January 10, 2018
PubMed

Insights

Hedgehog signaling modulation by cyclopamine and Shh altered drug resistance in U251-MG glioma cells, but not in human astrocytes. This research aids in understanding drug resistance mechanisms and personalizing chemotherapy.

Area of Science:

  • Neuro-oncology
  • Molecular biology
  • Pharmacology

Background:

  • Glioblastoma (U251-MG) exhibits significant drug resistance.
  • Hedgehog signaling pathway plays a role in various cancers.
  • Understanding drug resistance mechanisms is crucial for effective glioblastoma treatment.

Purpose of the Study:

  • To investigate the impact of Hedgehog signaling modulation on the drug resistance of U251-MG human glioma cells.
  • To determine if these effects extend to normal human astrocytes.
  • To explore the potential of targeting Hedgehog signaling in combination with chemotherapy.

Main Methods:

  • Treatment of U251-MG cells and human astrocytes with Hedgehog pathway modulator (cyclopamine, Shh).
  • Exposure to standard chemotherapy agents: cisplatin, temozolomide, and doxorubicin.
  • Assessment of changes in cellular drug resistance.

Main Results:

  • Cyclopamine (inhibitor) and Shh (activator) significantly modified the drug resistance of U251-MG glioma cells.
  • Neither cyclopamine nor Shh affected the drug resistance of normal human astrocytes.
  • The study identified differential effects of Hedgehog signaling on cancer cells versus normal cells.

Conclusions:

  • Hedgehog signaling modulation influences chemotherapy resistance specifically in glioma cells.
  • These findings suggest potential therapeutic strategies targeting the Hedgehog pathway in glioblastoma.
  • Experimental data can inform personalized chemotherapy selection for cancer patients.
Keywords:
Hedgehog signaling pathwayShh polypeptidecyclopaminedrug resistanceglioblastoma multiforme

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