JQ1, a small molecule inhibitor of BRD4, suppresses cell growth and invasion in oral squamous cell carcinoma

Background/Aims: Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first “Survivin suppressant” but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells. Methods: SCC9 and SCC25 were treated with different concentration of YM155 for indicated time. Using MTT assay and flow cytometry analysis to detect cell growth and apoptosis; Using transwell and Wound healing assay to detect migration and invasion; Using reverse transcription-PCR, Western blotting and electrophoretic mobility shift assay for measuring gene and protein expression, and DNA binding activity of NF-κB. Results: YM155 inhibited survivin-rich expressed SCC9 cell growth in a dose- and time dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-κB and downregulation of NF-κB downstream genes MMP-9, resulting in the inhibition of SCC9 cell migration and invasion in vitro and caused antitumor activity and anti metastasis in vivo. YM155 treatment did not affect cell growth, apoptosis and invasion of surviving-poor expressed SCC25 cells in vitro. Conclusions: YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin signaling processes. Our findings provide evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. We also suggest that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC.

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P3.17-003 A Selective Small Molecule Inhibitor of C-Met Kinase, BPI-9016M, Has Synergistic Effects with Radiation on Esophageal Squamous Cell Carcinoma

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.1949 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2364

Author(s):

Y. Xu ◽

C. Jiang ◽

S. Han ◽

G. Lin ◽

F. Gu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Small Molecule ◽

Squamous Cell ◽

Synergistic Effects ◽

Small Molecule Inhibitor ◽

Molecule Inhibitor

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Small Molecule Inhibitor of CBP/Beta-Catenin Signaling Enhanced Radiation Sensitivity in Head and Neck Squamous Cell Carcinoma

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0032-1312084 ◽

2012 ◽

Vol 73 (S 01) ◽

Author(s):

Vicky Yamamoto ◽

Rohit Khanna ◽

Michael Kahn ◽

Vijay Kalra ◽

Uttam Sinha

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Small Molecule ◽

Squamous Cell ◽

Radiation Sensitivity ◽

Small Molecule Inhibitor ◽

Neck Squamous Cell Carcinoma ◽

Beta Catenin ◽

Molecule Inhibitor

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From molecular diagnostics to molecular targeted therapy with natural product small molecule inhibitors in oral squamous cell carcinoma

Planta Medica ◽

10.1055/s-2007-986722 ◽

2007 ◽

Vol 73 (09) ◽

Cited By ~ 1

Author(s):

VB Konkimalla ◽

VL Suhas ◽

NR Chandra ◽

E Gebhart ◽

T Efferth

Keyword(s):

Squamous Cell Carcinoma ◽

Targeted Therapy ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Natural Product ◽

Molecular Diagnostics ◽

Small Molecule ◽

Squamous Cell ◽

Molecular Targeted Therapy ◽

Small Molecule Inhibitors

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PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02190-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ling Mao ◽

Xiaoweng Wu ◽

Zhengpeng Gong ◽

Ming Yu ◽

Zhi Huang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Growth ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Expression Pattern ◽

Cancer Progression ◽

Squamous Cell ◽

Aerobic Glycolysis ◽

Lactate Production ◽

Control Group

Abstract Background/objective Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC). Methods The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively. Results A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells. Conclusion This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.

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