Silencing stathmin-modulating efficiency of chemotherapy for esophageal squamous cell cancer with paclitaxel

Feng, Wen; Xing, Xuan; Yang, Xuan; Xiangke, L; Zichang, Y; Ran, Zhi Hua; Liuxing, W; Fan, Qingxia

doi:10.1038/cgt.2014.74

Cited by 25 publications

(20 citation statements)

References 26 publications

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“…Our results demonstrate for the first time that in the absence of additional polymerization promoter, intrinsic paclitaxel polymerizing activity is inhibited in the presence of stathmin. Our findings are consistent with recent clinical studies showing that high stathmin level are correlated with poor response or resistance to paclitaxel containing chemotherapy in endometrial or breast cancer [ 28 – 30 ] or reversely that functional knockdown of stathmin using siRNA results in increased sensitivity to paclitaxel [ 9 , 31 ].…”

Section: Discussionsupporting

confidence: 92%

Stathmin Potentiates Vinflunine and Inhibits Paclitaxel Activity

et al. 2015

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Cell biology and crystallographic studies have suggested a functional link between stathmin and microtubule targeting agents (MTAs). In a previous study we showed that stathmin increases vinblastine (VLB) binding to tubulin, and that conversely VLB increases stathmin binding to tubulin. This constituted the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and revealed a new mechanism of action for VLB. The question remained if the observed interaction was specific for this drug or represented a general phenomenon for all MTAs. In the present study we investigated the binding of recombinant stathmin to purified tubulin in the presence of paclitaxel or another Vinca alkaloid, vinflunine, using Isothermal Titration Calorimetry (ITC). These experiments revealed that stathmin binding to tubulin is increased in the presence of vinflunine, whereas no signal is observed in the presence of paclitaxel. Further investigation using turbidity and co-sedimentation showed that stathmin inhibited paclitaxel microtubule-stabilizing activity. Taken together with the previous study using vinblastine, our results suggest that stathmin can be seen as a modulator of MTA activity and binding to tubulin, providing molecular explanation for multiple previous cellular and in vivo studies showing that stathmin expression level affects MTAs efficiency.

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Section: Discussionsupporting

confidence: 92%

Stathmin Potentiates Vinflunine and Inhibits Paclitaxel Activity

et al. 2015

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“…Taxol is an effective antitumor chemotherapeutic agent derived from plants, which induces cell cycle arrest and cellular apoptosis by promoting MT polymerization (19)(20)(21). With the wide application of taxol in clinical practice, a large number of resistant tumors have emerged; therefore, high doses of taxol are increasingly prescribed, which results in severe side-effects.…”

Section: Discussionmentioning

confidence: 99%

The Cdc2/Cdk1 inhibitor, purvalanol A, enhances the cytotoxic effects of taxol through Op18/stathmin in non-small cell lung cancer cells in vitro

Chen

Liao

Long

et al. 2017

International Journal of Molecular Medicine

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Purvalanol A is a highly selective inhibitor of Cdc2 [also known as cyclin-dependent kinase 1 (CDK1)]. Taxol is an anti-tumor chemotherapeutic drug which is widely used clinically. In this study, the CDK1 inhibitor, purvalanol A was applied to explore the relevance of Cdc2 signaling and taxol sensitivity through analyses, such as cellular proliferation and apoptosis assays, ELISA, western blot analysis and immunoprecipitation. We demonstrated that purvalanol A effectively enhanced the taxol-induced apoptosis of NCI-H1299 cells, as well as its inhibitory effects on cellular proliferation and colony formation. In combination, purvalanol A and taxol mainly decreased the expression of oncoprotein 18 (Op18)/stathmin and phosphorylation at Ser16 and Ser38, while purvalanol A alone inhibited the phosphorylation of Op18/stathmin at all 4 serine sites. Co-treatment with purvalanol A and taxol weakened the expression of Bcl-2 and activated the extrinsic cell death pathway through the activation of caspase-3 and caspase-8. Further experiments indicated that Cdc2 kinase activities, including the expression of Cdc2 and the level of phospho-Cdc2 (Thr161) were significantly higher in taxol-resistant NCI-H1299 cells compared with the relatively sensitive CNE1 cells before and following treatment with taxol. These findings suggest that Cdc2 is positively associatd with the development of taxol resistance. The Cdc2 inhibitor, purvalanol A, enhanced the cytotoxic effects of taxol through Op18/stathmin. Our findings may prove to be useful in clinical practice, as they may provide a treatment strategy with which to to reduce the doses of taxol applied clinically, thus alleviating the side-effects.

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“…At present, paclitaxel is clinically used as the firstline treatment for breast cancer, lung cancer, esophageal cancer, colon cancer, lymphoma, acute leukemia, melanin, ovarian cancer and gastric cancer (Pitakkarnkul et al, 2013;Jianmin et al, 2014;Tanaka et al, 2014;Feng et al, 2015;Langer et al, 2015). However, it is hard to be absorbed by taking orally due to its physicochemical property, such as poor water solubility, so it is mostly…”

Section: Introductionmentioning

confidence: 99%