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Silencing stathmin-modulating efficiency of chemotherapy for esophageal squamous cell cancer with paclitaxel

Cancer Gene Therapy volume 22, pages 115–121 (2015)Cite this article

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Abstract

Paclitaxel (PTX) is broadly considered the drug of choice for treating human esophageal squamous cell cancer (ESCC). However, PTX resistance often ultimately leads to treatment failure. stathmin, or Op18, is a ubiquitously expressed 19-kDa cytosolic phosphoprotein that can integrate various cellular regulatory signals. stathmin overexpression could lead to resistance to chemotherapeutic agents. In this study we investigated the effect of stathmin gene silencing, using small interfering RNA (stathmin siRNA), on the efficacy of PTX in ESCC. Transfection of stathmin siRNA could significantly inhibit stathmin mRNA and protein levels in ESCC cell lines EC9706 and Eca-109. The silencing of stathmin combined with PTX significantly inhibited the proliferation of EC9706 and Eca-109 cells, with a significantly higher proportion of cells at G2/M phase and this antiproliferative effect was accompanied by an increase in apoptosis rates and morphology changes of EC9706 and Eca-109. Thus, combined chemotherapeutic agent PTX and stathmin siRNA could potentially enhance the therapeutic outcomes of PTX in treating ESCC.

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References

  1. Rasool S, Khan T, Qazi F, Ganai BA . ECRG1 and its relationship with esophageal cancer. Onkologie 2013; 36: 213.

    Article  CAS  Google Scholar 

  2. Zhu ML, Shi TY, Hu HC, He J, Wang M, Jin L et al. Polymorphisms in the ERCC5 gene and risk of esophageal squamous cell carcinoma (ESCC) in Eastern Chinese populations. PLoS One 2012; 7: e41500.

    Article  CAS  Google Scholar 

  3. Miyagaki H, Yamasaki M, Miyata H, Takahashi T, Kurokawa Y, Nakajima K et al. Overexpression of PFTK1 predicts resistance to chemotherapy in patients with oesophageal squamous cell carcinoma. Br J Cancer 2012; 106: 947.

    Article  CAS  Google Scholar 

  4. Zhou H, Zeng C, Wei Y, Zhou J, Yao W . Duration of chemotherapy for small cell lung cancer: a meta-analysis. PLoS One 2013; 8: e73805.

    Article  CAS  Google Scholar 

  5. Guido Bocci, Antonello Di Paolo, Romano Danesi . The pharmacological bases of the antiangiogenic activity of paclitaxel. Angiogenesis 2013; 16: 481.

    Article  Google Scholar 

  6. Schwarz . Superior antitumor activity of nanoparticle albumin- bound paclitaxel in experimental gastric cancer. PLoS One 2013; 8: e58037.

    Article  Google Scholar 

  7. Rubin CI, Atweh GF . The role of stathmin in the regulation of the cell cycle. J Cell Biochem 2004; 93: 242.

    Article  CAS  Google Scholar 

  8. Segerman B, Holmfeldt P, Morabito J, Cassimeris L, Gullberg M . Autonomous and phosphoeylation responsive microtubule regulating activities of the N-terminus of Opl8/stathnfin. J Cell Sci 2013; 116: 97.

    Google Scholar 

  9. Tapas M, Douglas AT, Honnappa S, Michel OS, Leslie W . Regulation of Microtubule Dynamic Instability in Vitro by Differentially Phosphorylated Stathmin. J Biol Chem 2009; 284: 15640.

    Article  Google Scholar 

  10. Curmi PA, Gavet O, Charbaut E, Ozon S, Lachkar-Colmerauer S, Manceau V et al. Stathmin and its phosphoprotein family: general properties, biochemical and functional interaction with tubulin. Cell Struct Funct 1999; 24: 345.

    Article  CAS  Google Scholar 

  11. Karst AM, Levanon K, Duraisamy S, Liu JF, Hirsch MS, Hecht JL et al. Stathmin 1, a marker of PI3K pathway activation and regulator of microtubule dynamics, is expressed in early pelvic serous carcinomas. Gynecol Oncol 2011; 123: 5.

    Article  CAS  Google Scholar 

  12. Yeap YY, Ng IH, Badrian B, Nguyen TV, Yip YY, Dhillon AS et al. C-Jun N-terminal kinase/c-Jun inhibits fibroblast proliferation by negatively regulating the levels of stathmin/oncoprotein 18. Biochem J 2010; 430: 345.

    Article  CAS  Google Scholar 

  13. Han ZX, Wang HM, Jiang G, Du XP, Gao XY, Pei DS et al. Overcoming paclitaxel resistance in lung cancer cells via dual inhibition of stathmin and Bcl-2. Cancer Biother Radiopharm 2013; 28: 398.

    Article  CAS  Google Scholar 

  14. McGrogan BT, Gilmartin B, Carney DN, McCann A . Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 1785; 96: 2008.

    Google Scholar 

  15. Li J, Tan Q, Yan M, Liu L, Lin H, Zhao F et al. miRNA-200c inhibits invasion and metastasis of human non-small cell lung cancer by directly targeting ubiquitin specific peptidase 25. Mol Cancer 2014; 13: 166.

    Article  Google Scholar 

  16. Xu X, Dai H, Zhao Y, Wang Y, Xu X, Qian Z et al. In vitro chemosensitivity assay of ascites in epithelial ovarian cancer. Eur J Gynaecol Oncol 2013; 34: 559.

    CAS  PubMed  Google Scholar 

  17. Chen J, Han H, Chen M, Xu XZ, Wang B, Shi LY et al. Inactivated sendai virus strain tianjin induces apoptosis in human breast cancer MDA-MB-231 Cells. Asian Pac J Cancer Prev 2014; 15: 5023.

    Article  Google Scholar 

  18. Zhou K, Ji H, Mao T, Bai Z . Effects of matrine on the proliferation and apoptosis of human medulloblastoma cell line D341. Int J Clin Exp Med 2014; 7: 911.

    PubMed  PubMed Central  Google Scholar 

  19. Wang Y, Cheng X, Wang P, Wang L, Fan J, Wang X et al. Investigating migration inhibition and apoptotic effects of Fomitopsis pinicola chloroform extract on human colorectal cancer SW-480 cells. PLoS One 2014; 9: e101303.

    Article  Google Scholar 

  20. Gao Z, Zhu M, Wu Y, Gao P, Qin Z, Wang H et al. Interferon-λ1 induces G1 phase cell cycle arrest and apoptosis in gastric carcinoma cells in vitro. Oncol Rep 2014; 32: 199.

    Article  Google Scholar 

  21. Teiger E, Than VD, Richard L, Wisnewsky C, Tea BS, Gaboury L et al. Apoptosis in pressure overload-induced heart hypertrophy in the rat. J Clin Invest 1996; 97: 2891.

    Article  CAS  Google Scholar 

  22. Ahmed AA, Wang X, Lu, Goldsmith, Le, Grandjean G et al. Modulating microtubule stability enhances the cytotoxic response of cancer cells to paclitaxel. Cancer Res 2011; 71: 5806.

    Article  CAS  Google Scholar 

  23. Yi-Fu He, Chu-Shu Ji, Bing Hu, Ping-Sheng Fan, Chang-Lu Hu, Feng-Shou Jiang et al. A phase II study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma. World J Gastroenterol 2013; 19: 5910.

    Article  Google Scholar 

  24. Danielle NR, Lynne C . Stathmin regulates centrosomal nucleation of microtubules and tubulin dimer/polymer partitioning. Mol Biol Cell 2009; 20: 3451.

    Article  Google Scholar 

  25. Xinyong T, Yufeng T, Nicolene S, Tinghuai W, Anna A . Birukova. Novel role of stathmin in microtubule-dependent control of endothelial permeability. FASEB J 2012; 26: 3862.

    Article  Google Scholar 

  26. Tapas M, Douglas AT, Srinivas H, Michel OS, Leslie W . Regulation of microtubule dynamic instability in vitro by differentially phosphorylated stathmin. J Biol Chem 2009; 284: 15640.

    Article  Google Scholar 

  27. Henrica MJW, Jone T, Mari KH, Elisabeth W, Lars AA, Even B et al. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer. PLoS One 2014; 9: e90141.

    Article  Google Scholar 

  28. Wang Y, Chen Q, Jin S, Deng W, Li S, Tong Q et al. Up-regulation of P-glycoprotein is involved in the increased paclitaxel resistance in human esophageal cancer radioresistant cells. Scand J Gastroenterol 2012; 47: 802.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grant support from the Medical Science and Technology Program of Henan Province. (13A320638).

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  1. W Feng and X Xiaoyan: These authors contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    W Feng, L Xiangke, Y Zichang, Z Ran, W Liuxing & F Qingxia

  2. Department of Microbiology and Immunology, Zhengzhou University, Zhengzhou, Henan, China

    X Xiaoyan & Y Xuan

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  1. W Feng
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Correspondence to F Qingxia.

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Feng, W., Xiaoyan, X., Xuan, Y. et al. Silencing stathmin-modulating efficiency of chemotherapy for esophageal squamous cell cancer with paclitaxel. Cancer Gene Ther 22, 115–121 (2015). https://doi.org/10.1038/cgt.2014.74

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  • DOI: https://doi.org/10.1038/cgt.2014.74

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