title: Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, No.324, Jingwu Road, Jinan, Shandong, 250021, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, No.324, Jingwu Road, Jinan, Shandong, 250021, People's Republic of China.
authors.forename: Javed
authors.initials: J
authors.lastname: Akhtar
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, No.324, Jingwu Road, Jinan, Shandong, 250021, People's Republic of China. wz620226@hotmail.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008938:Mitosis / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050777:Stathmin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin; D050257:Tubulin Modulators; D014747:Vinblastine; D017239:Paclitaxel
keywords: Antimicrotubule drugs; Esophageal squamous cell carcinoma; Resistance; Stathmin