Combined antitumor activity of cucurbitacin B and docetaxel in laryngeal cancer.
Combination therapy with multiple drugs is a common practice in the treatment of cancer. The promising clinical activity of docetaxel has promoted considerable interest in combining it with other antitumor agents. To determine whether cucurbitacin B can enhance chemosensitivity to docetaxel in laryngeal cancer, in the present study, we investigated the combined antitumor effect of cucurbitacin B with docetaxel on Hep-2, a human laryngeal cancer cell line. We treated Hep-2 cells with cucurbitacin B alone or in combination with docetaxel and evaluated cell growth, cell cycle distribution, and apoptosis using MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay, flow cytometry, and fluorescent microscopy. Our results showed that, in comparison with single agent treatment, the combination of cucurbitacin B and docetaxel produced greater efficacy in growth inhibition, cell cycle arrest at G2/M phase, and apoptosis induction. Measuring the modulation of regulators in the cell cycle, apoptosis and signal transductions by Western blot analysis showed that the combination effect of cucurbitacin B and docetaxel was due to suppress the expression of p-STAT3 (signal transducers and activators of transcription 3), Bcl-2, and cyclin B1. Moreover, our in vivo studies were reproduced in a mouse xenograft model, where, the combination of cucurbitacin B with docetaxel synergestively inhibited tumor growth. Together, this investigation suggests that cucurbitacin B combined with docetaxel may be a feasible strategy to enhance the effects of chemotherapy in patients with laryngeal cancer.
Liu
Tingyan
T
Department of Otolaryngology, Second Affiliated Hospital of China Medical University, Shenyang 110004, Liaoning, China.
Zhang
Meixia
M
Zhang
Hongliang
H
Sun
Chunyan
C
Yang
Xiaolin
X
Deng
Yihui
Y
Ji
Wenyue
W
D017304:Annexin A5 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007202:Indicators and Reagents; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D007202:Indicators and Reagents; D009363:Neoplasm Proteins; D043823:Taxoids; D014315:Triterpenes; C041246:cucurbitacin B; D000077143:Docetaxel