Title |
BCL-2 inhibition impairs mitochondrial function and targets oral tongue squamous cell carcinoma
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Published in |
SpringerPlus, September 2016
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DOI | 10.1186/s40064-016-3310-2 |
Pubmed ID | |
Authors |
Lei Xiong, Yi Tang, Zhaoyang Liu, Jing Dai, Xiaozhou Wang |
Abstract |
To understand the role of Bcl-2 overexpression in oral tongue squamous cell carcinoma (OTSCC) patients and investigate the efficacy of targeting Bcl-2 in OTSCC. The expression level of Bcl-2 on normal tongue cells and OTSCC cells were measured by real-time PCR and western blotting. The functional roles of Bcl-2 were examined by MTS, flow cytometry and xenograft cancer mouse model. Mechanism studies were performed by analyzing mitochondrial functions in a panel of OTSCC cell lines. Bcl-2 is up-regulated at mRNA and protein levels in a panel of OTSCC cell lines compared to normal tongue epithelial cells (NTEC). Importantly, overexpression of Bcl-2 confers resistance of OTSCC cells to chemotherapeutic drug cisplatin treatment. Overexpression of Bcl-2 in NTEC significantly increased cell growth. In contrast, inhibition of Bcl-2 by genetic and pharmacological approaches inhibits proliferation and induces apoptosis in OTSCC cells. Mechanistically, Bcl-2 inhibitor ABT-199 impairs mitochondrial functions as shown by the decreased levels of mitochondrial membrane potential, mitochondrial respiration and ATP, and the increased levels of ROS in OTSCC cells. In addition, ABT-199 inhibits proliferation and induces apoptosis and mitochondrial dysfunctions in NTEC cells, but to a less extent than in OTSCC cells. We further show that ABT-199 augments the effects of cisplatin in eliminating OTSCC cells in in vitro tongue cancer cellular system and in vivo tongue cancer xenograft mouse model. Inhibition of Bcl-2 effectively targets OTSCC cells through inhibiting proliferation and inducing apoptosis. Inhibition of Bcl-2 also augments the inhibitory effects of cisplatin in vitro and in vivo. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 22 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 5 | 23% |
Other | 3 | 14% |
Student > Ph. D. Student | 3 | 14% |
Unknown | 11 | 50% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 4 | 18% |
Biochemistry, Genetics and Molecular Biology | 2 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Medicine and Dentistry | 1 | 5% |
Neuroscience | 1 | 5% |
Other | 0 | 0% |
Unknown | 13 | 59% |