Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma.
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.
['Wang|Shuai|S|', 'Akhtar|Javed|J|', 'Wang|Zhou|Z|']
D000818:Animals D017209:Apoptosis D015153:Blotting, Western D002294:Carcinoma, Squamous Cell D002453:Cell Cycle D049109:Cell Proliferation D004938:Esophageal Neoplasms D005434:Flow Cytometry D005455:Fluorescent Antibody Technique D015972:Gene Expression Regulation, Neoplastic D020868:Gene Silencing D006801:Humans D007124:Immunoenzyme Techniques D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D008938:Mitosis D017239:Paclitaxel D012333:RNA, Messenger D060888:Real-Time Polymerase Chain Reaction D020133:Reverse Transcriptase Polymerase Chain Reaction D050777:Stathmin D050257:Tubulin Modulators D014407:Tumor Cells, Cultured D014747:Vinblastine D023041:Xenograft Model Antitumor Assays
Antimicrotubule drugs Esophageal squamous cell carcinoma Stathmin Resistance