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

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...

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Main Authors: Teoh, Hoon Koon, Chong, Pei Pei, Abdullah, Maha, Sekawi, Zamberi, Tan, Geok Chin, Leong, Chooi Fun, Cheong, Soon Keng
Format: Article
Language:English
Published: Elsevier 2016
Online Access:http://psasir.upm.edu.my/id/eprint/53832/1/Small%20interfering%20RNA%20silencing%20of%20interleukin-6%20in%20mesenchymal%20stromal%20cells%20inhibits%20multiple%20myeloma%20cell%20growth.pdf
http://psasir.upm.edu.my/id/eprint/53832/
http://www.lrjournal.com/article/S0145-2126(15)30396-9/fulltext
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spelling my.upm.eprints.538322018-02-12T01:46:25Z http://psasir.upm.edu.my/id/eprint/53832/ 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 Leong, Chooi Fun Cheong, Soon Keng 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. Elsevier 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/53832/1/Small%20interfering%20RNA%20silencing%20of%20interleukin-6%20in%20mesenchymal%20stromal%20cells%20inhibits%20multiple%20myeloma%20cell%20growth.pdf Teoh, Hoon Koon and Chong, Pei Pei and Abdullah, Maha and Sekawi, Zamberi and Tan, Geok Chin and Leong, Chooi Fun and Cheong, Soon Keng (2016) Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth. Leukemia Research, 40. pp. 44-53. ISSN 0145-2126, ESSN: 1873-5835 http://www.lrjournal.com/article/S0145-2126(15)30396-9/fulltext 10.1016/j.leukres.2015.10.004
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description 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.
format Article
author Teoh, Hoon Koon
Chong, Pei Pei
Abdullah, Maha
Sekawi, Zamberi
Tan, Geok Chin
Leong, Chooi Fun
Cheong, Soon Keng
spellingShingle Teoh, Hoon Koon
Chong, Pei Pei
Abdullah, Maha
Sekawi, Zamberi
Tan, Geok Chin
Leong, Chooi Fun
Cheong, Soon Keng
Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth
author_facet Teoh, Hoon Koon
Chong, Pei Pei
Abdullah, Maha
Sekawi, Zamberi
Tan, Geok Chin
Leong, Chooi Fun
Cheong, Soon Keng
author_sort Teoh, Hoon Koon
title Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth
title_short Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth
title_full Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth
title_fullStr Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth
title_full_unstemmed Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth
title_sort small interfering rna silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth
publisher Elsevier
publishDate 2016
url http://psasir.upm.edu.my/id/eprint/53832/1/Small%20interfering%20RNA%20silencing%20of%20interleukin-6%20in%20mesenchymal%20stromal%20cells%20inhibits%20multiple%20myeloma%20cell%20growth.pdf
http://psasir.upm.edu.my/id/eprint/53832/
http://www.lrjournal.com/article/S0145-2126(15)30396-9/fulltext
_version_ 1643835499101552640
score 13.211869

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