Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

29 October 2017 : Laboratory Research  

Effects of Histone Deacetylase Inhibitor Panobinostat (LBH589) on Bone Marrow Mononuclear Cells of Relapsed or Refractory Multiple Myeloma Patients and Its Mechanisms

Yanping Ma1ABCDEFG*, Wenhua Liu1BCDEF, Ling Zhang1BCDEF, Gu Jia1CDEF

DOI: 10.12659/MSM.904232

Med Sci Monit 2017; 23:5150-5157

Abstract

BACKGROUND: The aim of this study was to explore the impact of LBH589 alone or in combination with proteasome inhibitor bortezomib on multiple myeloma (MM) cell proliferation and its mechanism.

MATERIAL AND METHODS: MM cell line U266 and RRMM-BMMNC were treated with different concentrations of LBH589 alone or in combination with bortezomib. Cell proliferation was detected by MTT assay. Cell cycle and apoptosis was analyzed by flow cytometry. The protein and mRNA level of related genes was determined by Western blotting and qRT-PCR respectively.

RESULTS: U266 cell and RRMM-BMMNC proliferation were inhibited by different concentrations of LBH589 (0, 10, 20, and 50 nmol/L) alone or 50 nmol/L of LBH589 in combination with bortezomib (10 and 20 nmol/L) in a dose- and time-dependent manner. LBH589 significantly induced G0/G1phase arrest and apoptosis in RRMM-BMMNC in a dose-dependent manner. The effects were significantly higher in all combined groups than in single-agent groups (all P<0.05). The mRNA level of Caspase3 and APAF1 were up-regulated gradually, while TOSO gene expression in RRMM-BMMNC was down-regulated gradually in a dose- and time-dependent manner. Moreover, LBH589 significantly induced hyperacetylation of histone H4, the protein level of PARP notably increased, and the level of Bcl-X decreased.

CONCLUSIONS: LBH589 can inhibit MM cell growth, block the cell cycle, and induce cell apoptosis, which has an anti-resistant effect on multidrug-resistant cells. LBH589 in combination with bortezomib has a synergistic effect on myeloma cells; its mechanism and reversal of drug resistance mechanism is involved in multiple changes in gene expression.

Keywords: Multiple Myeloma

Add Comment 0 Comments

Editorial

01 February 2025 : Editorial  

Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-Smokers

Dinah V. Parums

DOI: 10.12659/MSM.948255

Med Sci Monit 2025; 31:e948255

0:00

In Press

Clinical Research  

Evaluation of Knowledge, Attitudes, and Practices Toward Thyroid Nodules in 456 Patients with Thyroid Nodules

Med Sci Monit In Press; DOI: 10.12659/MSM.945732  

Review article  

Comparative Efficacy of 3D-Printed Insoles in Managing Common Foot Conditions: A Review

Med Sci Monit In Press; DOI: 10.12659/MSM.947252  

Clinical Research  

Correlation Descriptive Study on Nurses' Professional Values and Job Satisfaction and the Ethical Climate o...

Med Sci Monit In Press; DOI: 10.12659/MSM.945639  

Clinical Research  

Pre- and Post-Surgical MRI Analysis of Levator Ani in Pelvic Organ Prolapse Patients: A Single-Center Study

Med Sci Monit In Press; DOI: 10.12659/MSM.945993  

Most Viewed Current Articles

17 Jan 2024 : Review article   6,967,723

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

16 May 2023 : Clinical Research   701,731

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Mar 2024 : Editorial   25,246

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...

DOI :10.12659/MSM.944204

Med Sci Monit 2024; 30:e944204

0:00

28 Jan 2024 : Review article   19,861

A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and Future

DOI :10.12659/MSM.943912

Med Sci Monit 2024; 30:e943912

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750