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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
IL-6 antisense-mediated growth inhibition in a head and neck squamous cell carcinoma cell line
Gregor Bran1, Karl Götte, Katrin Riedel
1Department of Otolaryngology, Head and Neck Surgery, University Hospital of Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. gregor.bran@umm.de
Abstract:
The growth of tumor cells can be regulated by a variety of cytokines. To investigate the pathogenesis of head and neck cancer and explore a new therapeutic approach for the carcinoma, the role of interleukin-6 (IL-6) in the growth of a human head and neck squamous cell carcinoma (HNSCC) cell line was examined. Whether or not IL-6 is increased in HNSCC and whether or not IL-6 antisense oligonucleotide treatment could decrease proliferation and angiogenic activity of HNSCC cell lines, was determined. Established human HNSCC cell lines were screened for IL-6 expression at both mRNA and protein levels. By using a 15-mer antisense phosphorothioate oligonucleotide targeting a sequence in the second exon of the IL-6 gene, modulation of IL-6 and vascular endothelial growth factor (VEGF) expression was examined in UMSCC IIA in cell supernatants by capture enzyme-linked immunosorbent assay (ELISA), and in cell lysates by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, cell growth was determined by cell count. Endothelial cell migration was measured using a modified Boyden chamber. IL-6 was identified in the supernatant of the cell culture medium, indicating that these cells secreted IL-6, and the mRNAs of IL-6 were shown to be present in the cell lysates. IL-6 antisense oligonucleotide treatment resulted in a significant reduction of IL-6 protein expression compared to the sense control. The antisense oligonucleotides targeting IL-6 mRNA, also, inhibited cell growth and IL-6 production as well as VEGF expression. The addition of conditioned medium from IL-6 antisense-treated tumor cells resulted in decreased endothelial cell migration and tubule formation. Taken together, these findings indicate that endogenous IL-6 plays an important role in the growth of HNSCC and exerts its action by an autocrine growth mechanism, and that therapeutic trials with antisense oligonucleotides targeted to IL-6 mRNA may have some value for the treatment of HNSCC due to a decrease of neovascularization.
Insights
Interleukin-6 (IL-6) fuels head and neck squamous cell carcinoma (HNSCC) growth. Targeting IL-6 with antisense oligonucleotides inhibits tumor cell proliferation and reduces blood vessel formation, offering a potential new therapy for HNSCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cytokines regulate tumor cell growth.
- Head and neck squamous cell carcinoma (HNSCC) pathogenesis requires further investigation.
- Interleukin-6 (IL-6) role in HNSCC is not fully understood.
Purpose of the Study:
- To investigate the role of IL-6 in HNSCC cell line growth.
- To determine if IL-6 is elevated in HNSCC.
- To explore IL-6 antisense oligonucleotide therapy for HNSCC.
Main Methods:
- Screened HNSCC cell lines for IL-6 mRNA and protein.
- Used IL-6 antisense oligonucleotides to modulate IL-6 and VEGF expression.
- Assessed cell proliferation, IL-6/VEGF levels, and endothelial cell migration.
Main Results:
- HNSCC cells secrete IL-6 and express IL-6 mRNA.
- IL-6 antisense treatment significantly reduced IL-6 protein and mRNA expression.
- Antisense treatment inhibited HNSCC cell growth, IL-6 production, and VEGF expression.
- Conditioned medium from treated cells decreased endothelial cell migration and tubule formation.
Conclusions:
- Endogenous IL-6 is crucial for HNSCC growth via autocrine mechanisms.
- IL-6 antisense oligonucleotide therapy may be valuable for HNSCC treatment.
- Therapeutic targeting of IL-6 can reduce HNSCC neovascularization.
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