Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin

Shen,Fang; Long,Dan; Yu,Ting; Chen,Xian; Liao,Ying; Wu,Yi; Lin,Xuechi

doi:10.3892/or.2017.5469

Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin

Authors:
- Fang Shen
- Dan Long
- Ting Yu
- Xian Chen
- Ying Liao
- Yi Wu
- Xuechi Lin
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Affiliations: Department of Medical Laboratory, Changsha Medical University, Changsha, Hunan 410219, P.R. China, Department of Clinical Laboratory, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410000, P.R. China
Published online on: February 20, 2017 https://doi.org/10.3892/or.2017.5469
Pages: 2481-2489

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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.

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