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Open AccessArticle

The Potential Impact of Connexin 43 Expression on Bcl-2 Protein Level and Taxane Sensitivity in Head and Neck Cancers–In Vitro Studies

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Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, H-1094 Budapest, Hungary
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MTA-SE Pathobiochemistry Research Group, Semmelweis University, H-1094 Budapest, Hungary
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Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, H-1083 Budapest, Hungary
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Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary
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Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
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Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, H-1097 Budapest, Hungary
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Oncompass Medicine Ltd, H-1024 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(12), 1848; https://doi.org/10.3390/cancers11121848
Received: 28 May 2019 / Revised: 8 November 2019 / Accepted: 20 November 2019 / Published: 22 November 2019
The poor prognosis of head and neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable predictive markers. Connexin 43 (Cx43) protein and its cell-communication channels have been assigned tumor suppressor functions while the anti-apoptotic Bcl-2 (B-cell lymphoma-2) protein has been associated with negative prognostic significance in cancer. This study aimed to test the role of Cx43 protein on Bcl-2 expression, tumor progression and response to taxane-based treatment in HNSCC. Human papillomavirus (HPV) negative HNSCC cell lines were tested for paclitaxel sensitivity through measuring apoptosis induction, cell viability and changes in Cx43 and Bcl-2 levels using flow cytometry, cell viability assay, immunocytochemistry and western blot. Inhibition of Cx43 expression using siRNA increased Bcl-2 protein levels in SCC25 (tongue squamous cell carcinoma) cells, while forced Cx43 expression reduced Bcl-2 levels and supported paclitaxel cytotoxicity in FaDu (hypopharynx squamous cell carcinoma) cells. In vitro results were in line with protein expression and clinicopathological features tested in tissue microarray samples of HNSCC patients. Our data demonstrate that elevated Cx43 and reduced Bcl-2 levels may indicate HNSCC sensitivity to taxane-based treatments. On the contrary, silencing of the Cx43 gene GJA1 (gap junction protein alpha-1) can result in increased Bcl-2 expression and reduced paclitaxel efficiency. Clinical tumor-based analysis also confirmed the inverse correlation between Cx43 and Bcl-2 expression. View Full-Text
Keywords: head and neck cancer; paclitaxel; connexin 43; Bcl-2 head and neck cancer; paclitaxel; connexin 43; Bcl-2
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Gurbi, B.; Brauswetter, D.; Varga, A.; Gyulavári, P.; Pénzes, K.; Murányi, J.; Zámbó, V.; Birtalan, E.; Krenács, T.; Becker, D.L.; Csala, M.; Vályi-Nagy, I.; Peták, I.; Dános, K. The Potential Impact of Connexin 43 Expression on Bcl-2 Protein Level and Taxane Sensitivity in Head and Neck Cancers–In Vitro Studies. Cancers 2019, 11, 1848.

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