Tumor Biology

, Volume 36, Issue 10, pp 7797–7806 | Cite as

Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma

  • Shuai Wang
  • Javed Akhtar
  • Zhou Wang
Research Article


Stathmin (STMN1) regulates microtubule dynamics by promoting depolymerization of microtubules and/or preventing polymerization of tubulin heterodimers. Several studies have shown that overexpression of STMN1 has been linked to chemoresistance of paclitaxel and vinblastine in tumor cells. This study aimed to investigate the effects of STMN1 silencing on chemosensitivities of paclitaxel or vinblastine in esophageal squamous cell carcinoma (ESCC). Immunocytochemistry and immunofluorescence assays showed that STMN1 gene was highly expressed in Eca109 and TE-1 cells. We demonstrated that lentiviral-mediated STMN1 short hairpin RNA (shRNA) specifically and efficiently downregulated STMN1 expression in Eca109 and TE-1 cells. The sensitivity of STMN1-silencing shRNA-transfected Eca109 and TE-1 cells increased 191.4- and 179.3-fold to paclitaxel, and 21.3- and 28.4-fold to vincristine, respectively. Flow cytometry and mitotic index assays showed that knockdown of STMN1 in Eca109 and TE-1 cells led to cell cycle arrest in G2/M phase. After treatment with paclitaxel or vincristine, STMN1-silencing shRNA-transfected Eca109 and TE-1 cells were more likely to enter G2 but less likely to enter mitosis than control cells. Therefore, these data suggests that silencing STMN1 gene could increase sensitivity of ESCC to paclitaxel and vincristine through G2/M phase block.


Esophageal squamous cell carcinoma Resistance Stathmin Antimicrotubule drugs 


Compliance with ethical standards

This study was carried out in strict accordance with the recommendations in the Guide for the Chinese Ethics Review Committees. The protocol was approved by the Ethics Committee of Provincial Hospital Affiliated to Shandong University.

Conflict of interest



  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Gao D, Hu J, Zhang X, Gao C, Hong J. Effect of hOGG1 over-expression on cisplatin resistance in esophageal squamous carcinoma cells. Cancer Biother Radiopharm. 2013;28:433–40.CrossRefPubMedGoogle Scholar
  3. 3.
    Alexander BM, Wang XZ, Niemierko A, Weaver DT, Mak RH, et al. DNA repair biomarkers predict response to neoadjuvant chemoradiotherapy in esophageal cancer. Int J Radiat Oncol Biol Phys. 2012;83:164–71.CrossRefPubMedGoogle Scholar
  4. 4.
    Giannakakou P, Villalba L, Li H, Poruchynsky M, Fojo T. Combinations of paclitaxel and vinblastine and their effects on tubulin polymerization and cellular cytotoxicity: characterization of a synergistic schedule. Int J Cancer. 1998;75:57–63.CrossRefPubMedGoogle Scholar
  5. 5.
    Ajani JA, Ilson DH, Daugherty K, Pazdur R, Lynch PM, et al. Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst. 1994;86:1086–91.CrossRefPubMedGoogle Scholar
  6. 6.
    Martello LA, Verdier-Pinard P, Shen H-J, He L, Torres K, et al. Elevated levels of microtubule destabilizing factors in a Taxol-resistant/dependent A549 cell line with an alpha-tubulin mutation. Cancer Res. 2003;63:1207–13.PubMedGoogle Scholar
  7. 7.
    Balachandran R, Welsh MJ, Day BW. Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells. Oncogene. 2003;22:8924–30.CrossRefPubMedGoogle Scholar
  8. 8.
    Alli E, Bash-Babula J, Yang J-M, Hait WN. Effect of Stathmin on the sensitivity to antimicrotubule drugs in human breast cancer. Cancer Res. 2002;62:6864–9.PubMedGoogle Scholar
  9. 9.
    Belmont L, Mitchison T. Catastrophic revelations about Op18/stathmin. Trends Biochem Sci. 1996;21:197–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Curmi PA, Andersen SSL, Lachkar S, Gavet O, Karsenti E, et al. The stathmin/tubulin interaction in vitro. J Biol Chem. 1997;272:25029–36.CrossRefPubMedGoogle Scholar
  11. 11.
    Sobel Jr A, AHT. Distinct patterns of cytoplasmic protein phosphorylation related to regulation of synthesis and release of prolactin by GH cells. J Biol Chem. 1983;258:10312–24.PubMedGoogle Scholar
  12. 12.
    Akhtar J, Wang Z, Yu C, Zhang ZP, Bi MM. STMN-1 Gene: a predictor of survival in stage IIA esophageal squamous cell carcinoma after Ivor-lewis esophagectomy? Ann Surg Oncol. 2014;21:315–21.CrossRefPubMedGoogle Scholar
  13. 13.
    Akhtar J, Wang Z, Jiang WP, Bi MM, Zhang ZP. Stathmin overexpression identifies high-risk of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma patients. J Gastroenterol Hepatol. 2014;29:944–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Akhtar J, Wang Z, Zhang ZP, Bi MM. Lentiviral-mediated RNA interference targeting stathmin1 gene in human gastric cancer cells inhibits proliferation in vitro and tumor growth in vivo. J Transl Med. 2013;11:212.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Rana S, Maples PB, Senzer N, Nemunaitis J. Stathmin 1. A novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther. 2008;8:1461–70.CrossRefPubMedGoogle Scholar
  16. 16.
    Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Rev Cancer. 2005;5:876–85.CrossRefPubMedGoogle Scholar
  17. 17.
    Sherbet GV, Cajone F. Stathmin in cell proliferation and cancer progression. Canc Genom Proteom. 2005;2:227–38.Google Scholar
  18. 18.
    Belletti B, Baldassarre G. Stathmin, a protein with many tasks. New biomarker and potential target in cancer. Expert Opin Ther Targets. 2011;15:1249–66.CrossRefPubMedGoogle Scholar
  19. 19.
    Alli E, Yang J-M, Ford JM, Hait WN. Reversal of stathmin-mediated resistance to paclitaxel and vinblastine in human breast carcinoma cells. Mol Pharmacol. 2007;71:1233-–40.CrossRefPubMedGoogle Scholar
  20. 20.
    Mitra M, Kandalam M, Sundaram CS, Verma RS, Maheswari UK, et al. Reversal of stathmin-mediated microtubule destabilization sensitizes retinoblastoma cells to a low dose of antimicrotubule agents: a novel synergistic therapeutic intervention. Invest Ophthalmol Vis Sci. 2011;52:5441–8.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Thoracic SurgeryProvincial Hospital Affiliated to Shandong UniversityJinanChina

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