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TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma

The treatment of renal cell carcinoma (RCC) with chemotherapy remains a challenge; therefore, improving the knowledge of the molecular mechanisms underlying RCC chemoresistance and developing novel therapeutic strategies is important. Dedicator of cytokinesis 1 (DOCK1), the first member of the DOCK...

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Autores principales: Zhang, Wei, Zheng, Xiaoxiao, Xie, Shangzhi, Zhang, Shufen, Mao, Jiayan, Cai, Ying, Lu, Xuemei, Chen, Wei, Ni, Haibin, Xie, Liping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339706/
https://www.ncbi.nlm.nih.gov/pubmed/32626999
http://dx.doi.org/10.3892/mmr.2020.11243
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author Zhang, Wei
Zheng, Xiaoxiao
Xie, Shangzhi
Zhang, Shufen
Mao, Jiayan
Cai, Ying
Lu, Xuemei
Chen, Wei
Ni, Haibin
Xie, Liping
author_facet Zhang, Wei
Zheng, Xiaoxiao
Xie, Shangzhi
Zhang, Shufen
Mao, Jiayan
Cai, Ying
Lu, Xuemei
Chen, Wei
Ni, Haibin
Xie, Liping
author_sort Zhang, Wei
collection PubMed
description The treatment of renal cell carcinoma (RCC) with chemotherapy remains a challenge; therefore, improving the knowledge of the molecular mechanisms underlying RCC chemoresistance and developing novel therapeutic strategies is important. Dedicator of cytokinesis 1 (DOCK1), the first member of the DOCK family to be discovered, displays various roles during tumorigenesis; however, its role during RCC progression is not completely understood. Therefore, the present study aimed to clarify the function of DOCK1 and 1-[2-(3′-(trifluoromethyl)-(1,1′-biphenyl)-4-yl)-2-oxoethyl]-5-pyrrolidinylsulfonyl-2 (1H)-pyridone (TBOPP), a DOCK1-sensitive inhibitor, during RCC development and chemoresistance. The results of CCK-8 and EdU assay indicated that TBOPP decreased RCC cell viability and proliferation compared with the control group, and sensitized RCC cells to cisplatin. Moreover, RCC cells with high DOCK1 expression levels displayed increased resistance to cisplatin, whereas DOCK1 knockdown enhanced the lethal effects of cisplatin on RCC cells. Furthermore, the results determined by western blotting, CCK-8 and cell apoptosis assay indicated that TBOPP effectively reduced DOCK1 expression levels compared with the control group, and the TBOPP-mediated cisplatin sensitizing effect was mediated by DOCK1 inhibition. The present study suggests that DOCK1 plays a vital role in RCC cell chemoresistance to cisplatin; therefore, TBOPP may serve as a novel therapeutic agent for RCC chemoresistance.
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spelling pubmed-73397062020-07-09 TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma Zhang, Wei Zheng, Xiaoxiao Xie, Shangzhi Zhang, Shufen Mao, Jiayan Cai, Ying Lu, Xuemei Chen, Wei Ni, Haibin Xie, Liping Mol Med Rep Articles The treatment of renal cell carcinoma (RCC) with chemotherapy remains a challenge; therefore, improving the knowledge of the molecular mechanisms underlying RCC chemoresistance and developing novel therapeutic strategies is important. Dedicator of cytokinesis 1 (DOCK1), the first member of the DOCK family to be discovered, displays various roles during tumorigenesis; however, its role during RCC progression is not completely understood. Therefore, the present study aimed to clarify the function of DOCK1 and 1-[2-(3′-(trifluoromethyl)-(1,1′-biphenyl)-4-yl)-2-oxoethyl]-5-pyrrolidinylsulfonyl-2 (1H)-pyridone (TBOPP), a DOCK1-sensitive inhibitor, during RCC development and chemoresistance. The results of CCK-8 and EdU assay indicated that TBOPP decreased RCC cell viability and proliferation compared with the control group, and sensitized RCC cells to cisplatin. Moreover, RCC cells with high DOCK1 expression levels displayed increased resistance to cisplatin, whereas DOCK1 knockdown enhanced the lethal effects of cisplatin on RCC cells. Furthermore, the results determined by western blotting, CCK-8 and cell apoptosis assay indicated that TBOPP effectively reduced DOCK1 expression levels compared with the control group, and the TBOPP-mediated cisplatin sensitizing effect was mediated by DOCK1 inhibition. The present study suggests that DOCK1 plays a vital role in RCC cell chemoresistance to cisplatin; therefore, TBOPP may serve as a novel therapeutic agent for RCC chemoresistance. D.A. Spandidos 2020-08 2020-06-16 /pmc/articles/PMC7339706/ /pubmed/32626999 http://dx.doi.org/10.3892/mmr.2020.11243 Text en Copyright: © Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhang, Wei
Zheng, Xiaoxiao
Xie, Shangzhi
Zhang, Shufen
Mao, Jiayan
Cai, Ying
Lu, Xuemei
Chen, Wei
Ni, Haibin
Xie, Liping
TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma
title TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma
title_full TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma
title_fullStr TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma
title_full_unstemmed TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma
title_short TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma
title_sort tbopp enhances the anticancer effect of cisplatin by inhibiting dock1 in renal cell carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339706/
https://www.ncbi.nlm.nih.gov/pubmed/32626999
http://dx.doi.org/10.3892/mmr.2020.11243
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