Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth

Hoon Koon Teoh, Pei Pei Chong, Maha Abdullah, Zamberi Sekawi, Geok Chin Tan, Leong Chooi Fun, Soon Keng Cheong

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Studies demonstrated that mesenchymal stromal cells (MSC) from bone marrow stroma produced high concentration of interleukin-6 (IL-6) that promoted multiple myeloma cell growth. In view of the failure of IL-6 monoclonal antibody therapy to demonstrate substantial clinical responses in early clinical trials, more effective methods are needed in order to disrupt the favourable microenvironment provided by the bone marrow stroma. In this study, we evaluated the short interfering RNA (siRNA)-mediated silencing of IL-6 in MSC and the efficacy of these genetically modified MSC, with IL-6 suppression, on inhibition of U266 multiple myeloma cell growth. IL-6 mRNA and protein were significantly suppressed by 72. h post IL-6 siRNA transfection without affecting the biological properties of MSC. Here we show significant inhibition of cell growth and IL-6 production in U266 cells co-cultured with MSC transfected with IL-6 siRNA when compared to U266 cells co-cultured with control MSC. We also show that the tumour volume and mitotic index of tumours in nude mice co-injected with U266 and MSC transfected with IL-6 siRNA were significantly reduced compared to tumours of mice co-injected with control MSC. Our results suggest potential use of RNA interference mediated therapy for multiple myeloma.

Original languageEnglish
JournalLeukemia Research
DOIs
Publication statusAccepted/In press - 15 Apr 2015

Fingerprint

RNA Interference
Multiple Myeloma
Mesenchymal Stromal Cells
Small Interfering RNA
Interleukin-6
Growth
Cultured Cells
Bone Marrow
Mitotic Index
Tumor Burden
Nude Mice
Transfection
Neoplasms
Monoclonal Antibodies
Clinical Trials
Messenger RNA
Therapeutics

Keywords

  • Interleukin-6
  • Mesenchymal stromal cells
  • Multiple myeloma
  • RNA interference
  • SiRNA

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth. / Teoh, Hoon Koon; Chong, Pei Pei; Abdullah, Maha; Sekawi, Zamberi; Tan, Geok Chin; Chooi Fun, Leong; Cheong, Soon Keng.

In: Leukemia Research, 15.04.2015.

Research output: Contribution to journalArticle

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