title: Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin.
abstract: Taxol (paclitaxel) and vinblastine (VBL) are both efficacious chemotherapeutic agents that target the microtubules of tumor cells, but each functions in a mutual antagonistic manner. Op18/stathmin is a small molecular phosphoprotein which promotes depolymerization of microtubules. Non-small cell lung cancer (NSCLC) NCI-H1299 cells were employed to compare the curative effects of VBL and Taxol and explore the correlation between drug sensitivity and Op18/stathmin signaling. The present study found that VBL obviously promoted cellular apoptosis and initiated activation of caspase 3 and 9, and inhibited cell proliferation and colony formation, as well as cell migration in the NCI-H1299 cells in contrast with Taxol. VBL did not affect the expression of Op18/stathmin, but increased its phosphorylation at all 4 serine sites. Conversely, Taxol mainly decreased the expression of Op18/stathmin and the phosphorylation at Ser25 and Ser63 sites. Silencing of Op18/stathmin by RNA interference (RNAi) led to a great reduction in the differences in the cell proliferation inhibition between VBL and Taxol. VBL treatment notably weakened the expression of PP2A, Bcl-2, NF-κB and interleukin-10 (IL-10) and autocrine IL-10 compared with Taxol; whereas PP2A was substantially increased following Taxol induction. High expression of Op18/stathmin was found to be negatively correlated with the sensitivity of Taxol in the NSCLC cells, but had a minor impact on VBL cytotoxicity. These findings revealed that both VBL and Taxol induce cell apoptosis through Op18/stathmin, but the mechanisms are completely different. VBL is an attractive alternative to the treatment of Taxol-resistant tumors with high expression of Op18/stathmin.
authors.affiliation: Department of Medical Laboratory, Changsha Medical University, Changsha, Hunan 410219, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Medical Laboratory, Changsha Medical University, Changsha, Hunan 410219, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.affiliation: Department of Medical Laboratory, Changsha Medical University, Changsha, Hunan 410219, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Medical Laboratory, Changsha Medical University, Changsha, Hunan 410219, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Laboratory, Changsha Medical University, Changsha, Hunan 410219, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410000, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Medical Laboratory, Changsha Medical University, Changsha, Hunan 410219, P.R. China.
authors.forename: Xuechi
authors.initials: X
authors.lastname: Lin
mesh_terms: D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D050777:Stathmin / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology*
chemical_list: D050777:Stathmin; D014747:Vinblastine; D017239:Paclitaxel