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Ruxolitinib Regulates the Autophagy Machinery in Multiple Myeloma Cells

Alican Kusoglu1, Bakiye G Bagca1, Neslihan P O Ay1

  • 1Department of Medical Biology, Ege University Medical School, Izmir, Turkey.

Anti-Cancer Agents in Medicinal Chemistry
|February 19, 2020
PubMed
Abstract

Insights

Ruxolitinib shows anticancer effects in multiple myeloma cells by impacting the IL-6/JAK/STAT pathway and autophagy. This JAK1/2 inhibitor demonstrates potential as a targeted therapy for hematological malignancies.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Ruxolitinib, a JAK1/2 inhibitor, is FDA-approved for myelofibrosis.
  • The Interleukin-6/Janus Kinase/Signal Transducer and Activator of Transcription (IL-6/JAK/STAT) pathway is a therapeutic target in multiple myeloma due to its association with poor prognosis.

Purpose of the Study:

  • To investigate the potential anticancer effects of ruxolitinib on the ARH-77 multiple myeloma cell line.
  • To compare the effects of ruxolitinib on multiple myeloma cells versus healthy B lymphocytes (NCI-BL 2171 cell line).

Main Methods:

  • Cytotoxicity was assessed using the WST-1 assay.
  • Autophagosome formation was measured to investigate autophagy.
  • Apoptosis was analyzed via Annexin V-FITC staining and flow cytometry.
  • Gene expression changes in the IL-6/JAK/STAT pathway were analyzed using RT-qPCR.

Main Results:

  • Ruxolitinib exhibited IC50 values of 20.03 μM in ARH-77 cells and 33.9 μM in NCI-BL 2171 cells at 72 hours.
  • Ruxolitinib induced significant autophagosome accumulation in both cell lines.
  • Ruxolitinib treatment led to decreased expression of key genes including IL-6, IL-18, JAK2, TYK2, and AKT.

Conclusions:

  • Ruxolitinib demonstrates potential as a therapeutic agent for multiple myeloma by regulating the IL-6/JAK/STAT pathway.
  • Ruxolitinib interferes with the autophagy mechanism in multiple myeloma cells, suggesting a multifaceted mechanism of action.
Keywords:
Interleukin-6JAKRuxolitinibSTATautophagymultiple myeloma

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