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Updated: Dec 27, 2025

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
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Synergistic Apoptotic Effects of Bortezomib and Methylstat on Multiple Myeloma Cells

Fatma Necmiye Kacı1, Yağmur Kiraz1, Demet Çekdemir2

  • 1Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir, Turkey.

Archives of Medical Research
|March 1, 2020
PubMed
Abstract

Insights

This study found that combining methylstat and bortezomib synergistically kills multiple myeloma (MM) cells by inducing apoptosis and reducing proliferation. Methylstat shows potential as a new MM treatment agent.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multiple myeloma (MM) is a hematological malignancy.
  • Current treatments face challenges with resistance and toxicity.
  • Novel therapeutic strategies are continuously being explored.

Purpose of the Study:

  • To investigate the synergistic cytotoxic and apoptotic effects of methylstat in combination with bortezomib.
  • To evaluate the impact of this combination on U266 and ARH77 multiple myeloma cell lines.

Main Methods:

  • Cytotoxicity assessed via MTT assay.
  • Apoptosis evaluated using JC-1 assay for mitochondrial membrane potential, caspase-3 activity assays, and Annexin-V/PI staining via flow cytometry.
  • Gene expression analysis of apoptotic and antiapoptotic genes performed using qRT-PCR.

Main Results:

  • The combination of methylstat and bortezomib demonstrated synergistic antiproliferative and apoptotic effects on MM cells.
  • Combined treatment led to increased mitochondrial membrane potential loss, elevated caspase-3 activity, and phosphatidylserine externalization.
  • Cell cycle analysis revealed S-phase arrest, and methylstat modulated key apoptotic and antiapoptotic gene expressions.

Conclusions:

  • Bortezomib combined with methylstat significantly reduces proliferation and induces apoptosis in multiple myeloma cells.
  • Methylstat exhibits potential as a novel therapeutic agent for MM treatment, warranting further in vivo investigation.
Keywords:
ApoptosisBortezomibMethylstatMultiple myeloma

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