Op18/Stathmin Is Involved in the Resistance of Taxol Among Different Epithelial Carcinoma Cell Lines

Lin, Xiao; Liao, Ying; Xie, Juan; Liu, Shuangling; Su, Lichao; Zou, Haijiao

doi:10.1089/cbr.2014.1649

Cited by 16 publications

(22 citation statements)

References 31 publications

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“…In a previous study, we found that Epstein-Barr virusspecific protein-latent membrane protein 1 (LMP1) regulates the Op18/stathmin signaling pathway by mediating Cdc2, which accelerates cell cycle progression and promotes cell proliferation (16). In another recent study of ours, we confirmed that human NCI-H1299 non-small cell lung cancer cells highly expressing Op18/stathmin were the most highly resistant to taxol among 5 different cancer cells originating from epithelia, including CNE1, Hep3B-2, MGC, MCF-7 and NCI-H1299 (17).…”

Section: Introductionsupporting

confidence: 59%

“…Both the CNE1 cells and NCI-H1299 cells were a kind gift from Professor Ya Cao from the Cancer Research Institute of Central South University and cultured in RPMI-1640 (Gibco-BRL, Grand Island, NY, USA) with 10% fetal bovine serum (FBS; HyClone, Logan, UT, USA), 100 IU/ml penicillin and 100 µg/ml streptomycin at 37˚C, 5% CO 2 . CNE1 human cancer cells were testified to be the most sensitive to taxol among 5 various epithelial-deriving tumor cells in our previous study (17). Thus, they were used in this study for a comparison to the NCI-H1299 cells.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Introductionsupporting

confidence: 59%

Section: Methodsmentioning

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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“…Chemoresistance to docetaxel with stathmin overexpression may be caused by the microtubule‐destabilizing activity of stathmin, which may diminish binding to docetaxel and increase binding to vincristine‐like drugs . Chemoresistance to cisplatin and 5‐fluorouracil with stathmin overexpression may be caused by the participation of stathmin overexpression in the cellular response to DNA damage and caspase‐6‐mediated cellular apoptosis, as described in previous studies conducted in head and neck cancer or colorectal cancer, respectively . To some extent, these reasons lead to the unsatisfactory clinical benefit of TPF induction chemotherapy in OSCC patients with high stathmin expression.…”

Section: Discussionmentioning

confidence: 93%

“…Our previous study suggested that stathmin acts as an oncogene and could be a potential antitumor therapeutic biomarker in OSCC . Several studies have shown that overexpression of stathmin influences the resistance of docetaxel and cisplatin . Based on the above findings, a new therapy regimen targeting stathmin looks promising and needs to be researched.…”

Section: Introductionmentioning

confidence: 97%

Stathmin guides personalized therapy in oral squamous cell carcinoma

Long

Zhao

et al. 2020

Cancer Science

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The survival benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy in oral squamous cell carcinoma (OSCC) patients is not satisfactory.Previously, we identified that stathmin, a microtubule-destabilizing protein, is overexpressed in OSCC. Here, we further investigated its role as a biomarker that impacts on OSCC chemosensitivity. We analyzed the predictive value of stathmin on TPF induction chemotherapy and its impact on OSCC cell chemosensitivity. Then, we further investigated the therapeutic effects of the combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors in vitro and in vivo. We found that OSCC patients with low stathmin expression benefited from TPF induction chemotherapy, while OSCC patients with high stathmin expression could not benefit from TPF induction chemotherapy. Stathmin overexpression promoted cellular proliferation and decreased OSCC cell sensitivity to TPF treatment. In addition, inhibition of the PI3K-AKT-mTOR signaling pathway decreased stathmin expression and phosphorylation.The combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors exhibited a potent antitumor effect both in vitro and in vivo. Therefore, stathmin can be used as a predictive biomarker for TPF induction chemotherapy and a combination therapy regimen based on stathmin expression might improve the survival of OSCC patients. K E Y W O R D Sbiomarker, induction chemotherapy, oral squamous cell carcinoma, personalized therapy, translational medicine

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“…Although STMN1 over-expression has been reported to be positively correlated with lymph node metastasis and TNM staging [36, 37, 40], no association was proved in our study, which may be attributed to small sample size and different detection methods. Moreover, studies imply that cancer patients with low expression of STMN1 mRNA will have a favorable clinical efficacy after being treated with Taxol regimens [41, 42]. Silencing STMN1 enhances the sensitivity of gastric cancer cells to docetaxel, with the resistance index reducing to 3.41 [13].…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer

et al. 2017

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BackgroundIndividualized therapeutic regimen is a recently intensively pursued approach for targeting diseases, in which the search for biomarkers was considered the first and most important. Thus, the goal of this study was to investigate whether the UGT1A1, ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A genes are underlying biomarkers for gastric cancer, which, to our knowledge, has not been performed.MethodsNinety-eight tissue specimens were collected from gastric cancer patients between May 2012 and March 2015. A multiplex branched DNA liquidchip technology was used for measuring the mRNA expressions of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A. Direct sequencing was performed for determination of UGT1A1 polymorphisms. Furthermore, correlations between gene expressions, polymorphisms and clinicopathological characteristics were investigated.ResultsThe expressions of TYMS, TUBB3 and STMN1 were significantly associated with the clinicopathological characteristics of age, gender and family history of gastric cancer, but not with differentiation, growth patterns, metastasis and TNM staging in patients with gastric cancer. No clinical characteristics were correlated with the expressions of ERCC1, BRCA1, RRM1 and TOP2A. Additionally, patients carrying G allele at −211 of UGT1A1 were predisposed to developing tubular adenocarcinoma, while individuals carrying 6TAA or G allele respectively at *28 or −3156 of UGT1A1 tended to have a local invasion.ConclusionsThe UGT1A1 polymorphism may be useful to screen the risk population of gastric cancer, while TYMS, TUBB3 and STMN1 may be potential biomarkers for prognosis and chemotherapy guidance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0561-x) contains supplementary material, which is available to authorized users.

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Op18/Stathmin Is Involved in the Resistance of Taxol Among Different Epithelial Carcinoma Cell Lines

Cited by 16 publications

References 31 publications

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

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

Stathmin guides personalized therapy in oral squamous cell carcinoma

Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer

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