Cucurbitacin B, a small molecule inhibitor of the Stat3 signaling pathway, enhances the chemosensitivity of laryngeal squamous cell carcinoma cells to cisplatin.
We have previously shown that the simultaneous exposure of Hep-2 cells to cucurbitacin B and docetaxel significantly enhances anticancer activity of these cells by suppressing Stat3 activation and down-regulating the expression levels of key cell cycle and anti-apoptosis regulators. In order to determine whether cucurbitacin B can also enhance the sensitivity of Hep-2 laryngeal cells to cisplatin, we treated Hep-2 cells with either cucurbitacin B, cisplatin, or the combination and evaluated these cells for proliferation, cell cycle distribution, and apoptosis. Our results demonstrate that, in comparison to single agent cucurbitacin B or cisplatin treated cells, Hep-2 cells treated with a cucurbitacin B/cisplatin combination display synergistic effects on growth inhibition, cell cycle arrest, and apoptosis induction. Western blot analysis using protein extracts from Hep-2 cells treated with cucurbitacin B, cisplatin, or the combination largely recapitulated the observations made when treated with the cucurbitacin B/docetaxel combination. More specifically, Hep-2 cell lines treated with the cucurbitacin B/cisplatin combination demonstrated a significantly reduced level of p-Stat3 in comparison with single agent treated cells. In addition, cucurbitacin B/cisplatin treated Hep-2 cells also demonstrated a significant reduction in Bcl-2 and Cyclin B1 protein levels compared to single agent cucurbitacin B or cisplatin treated cells. Xenograft models containing Hep-2 cells in mice also demonstrated that this cucurbitacin B/cisplatin combination led to the synergistic inhibition of tumor growth. Taken together, these results suggest that the cucurbitacin B/cisplatin combination treatment may be a potentially useful therapeutic option for individuals diagnosed with laryngeal cancer.
Liu
Tingyan
T
Department of Otolaryngology, Affiliated Hospital of Hangzhou Normal University, No.126 Wenzhou Road, Hangzhou, Zhejiang, China.
Peng
Huaguang
H
Zhang
Meixia
M
Deng
Yihui
Y
Wu
Zhenghu
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D056744:Cyclin B1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D056744:Cyclin B1; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D014315:Triterpenes; C041246:cucurbitacin B; D002945:Cisplatin