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Updated: Aug 26, 2025

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

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[IL-6 Regulates the Chemosensitivity of Drug-Resistant Multiple Myeloma Cell Lines to Bortezomib through STAT3/Notch

Ying Liu1, Jing-Zhe Sui2, Li-Hua Zhu3

  • 1Department of Hematology, The First Affiliated Hospital of Guangxi Medical University;Nanning 530021, Guangxi Zhuang Autonomous Region, China.

Zhongguo Shi Yan Xue Ye Xue Za Zhi
|October 8, 2022
PubMed
Abstract

Insights

Interleukin-6 (IL-6) increases resistance to bortezomib (BTZ) in multiple myeloma (MM). Blocking IL-6 enhances BTZ chemosensitivity by downregulating the STAT3/Notch pathway.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled proliferation of plasma cells.
  • Drug resistance, particularly to proteasome inhibitors like bortezomib (BTZ), remains a significant challenge in MM treatment.
  • Interleukin-6 (IL-6) is a pleiotropic cytokine implicated in MM pathogenesis and drug resistance.

Purpose of the Study:

  • To investigate the role of IL-6 in bortezomib (BTZ) resistance in multiple myeloma (MM) cell lines.
  • To elucidate the underlying molecular mechanisms by which IL-6 influences BTZ chemosensitivity.
  • To evaluate the therapeutic potential of antagonizing IL-6 in overcoming BTZ resistance.

Main Methods:

  • Peripheral blood samples and human MM cell lines (KM3, KM3/BTZ) were utilized.
  • ELISA, CCK-8 assays, flow cytometry, and qRT-PCR were employed to assess IL-6 levels, drug sensitivity, cell cycle, apoptosis, and gene expression.
  • Western blotting was used to determine protein expression levels of IL-6, Notch1, and STAT3.

Main Results:

  • Elevated IL-6 levels were observed in BTZ-resistant MM patients and cell lines.
  • KM3/BTZ cells exhibited significantly reduced sensitivity to BTZ compared to KM3 cells.
  • Combined treatment with an IL-6 neutralizing antibody and BTZ demonstrated enhanced inhibition of proliferation, cell cycle arrest, apoptosis induction, and downregulation of IL-6, Notch1, and STAT3 signaling.

Conclusions:

  • Antagonizing IL-6 significantly enhances the chemosensitivity of multiple myeloma cells to bortezomib.
  • IL-6 contributes to BTZ resistance in MM, potentially through the STAT3/Notch signaling pathway.
  • Targeting IL-6 represents a promising strategy to overcome bortezomib resistance in multiple myeloma.
Keywords:
bortezomibchemosensitivityinterleukin-6multiple myeloma

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