[Norcantharidin potentialize the chemosensitivity of adriamycin through the NF-κB/IκBα signaling pathway]

Xiao-ning Song1, Heng-fei Du, Lu-jia Yu

  • 1Department of Hematology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.

Abstract

Insights

Norcantharidin (NCTD) enhances adriamycin (ADR) effectiveness against multiple myeloma (MM) cells by promoting apoptosis and reducing proliferation. This synergy involves regulating the NF-κB/IκBα pathway and key related genes.

Area of Science:

  • Pharmacology and Molecular Biology
  • Cancer Research
  • Hematology

Background:

  • Multiple myeloma (MM) is a hematological malignancy with limited treatment options.
  • Adriamycin (ADR) is a chemotherapeutic agent used in MM treatment.
  • Norcantharidin (NCTD) is a derivative with potential anti-cancer properties.

Purpose of the Study:

  • To investigate the synergistic effects of NCTD and ADR on MM cell proliferation and apoptosis.
  • To elucidate the underlying molecular mechanisms, including the NF-κB signaling pathway.

Main Methods:

  • U266 MM cells were treated with NCTD alone or in combination with ADR.
  • Cell viability and apoptosis were assessed using MTT assays and Annexin V/PI staining.
  • Protein expression of NF-κB P65, p-NF-κB p65, IκBα, p-IκBα, survivin, Bcl-2, and Bax was analyzed by Western blot.
  • Vascular endothelial growth factor (VEGF) expression was evaluated using immunohistochemistry.

Main Results:

  • NCTD significantly potentiated ADR's cytotoxicity and pro-apoptotic effects, demonstrating a synergistic anti-proliferation effect.
  • The combination downregulated nuclear NF-κB P65 and cytoplasmic p-IκBα, while cytoplasmic NF-κB P65 and IκBα remained unchanged.
  • Expression of survivin and Bcl-2 decreased, while Bax expression increased in the combination group compared to ADR alone.
  • NCTD enhanced ADR's inhibitory effect on VEGF expression.

Conclusions:

  • NCTD potentiates the chemosensitivity of multiple myeloma cells to ADR.
  • The synergistic effect is mediated through the regulation of the NF-κB/IκBα signaling pathway.
  • NCTD modulates NF-κB-regulated genes, including survivin, Bcl-2, Bax, and VEGF, contributing to enhanced anti-cancer activity.

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