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An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can...

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Autores principales: Lin, Chang-Ni, Tsai, Yi-Cheng, Hsu, Ching-Cheng, Liang, Yu-Ling, Wu, Yi-Ying, Kang, Chieh-Yi, Lin, Chun-Hong, Hsu, Pang-Hung, Lee, Gwo-Bin, Hsu, Keng-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868721/
https://www.ncbi.nlm.nih.gov/pubmed/33614227
http://dx.doi.org/10.1016/j.omtn.2020.12.025
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author Lin, Chang-Ni
Tsai, Yi-Cheng
Hsu, Ching-Cheng
Liang, Yu-Ling
Wu, Yi-Ying
Kang, Chieh-Yi
Lin, Chun-Hong
Hsu, Pang-Hung
Lee, Gwo-Bin
Hsu, Keng-Fu
author_facet Lin, Chang-Ni
Tsai, Yi-Cheng
Hsu, Ching-Cheng
Liang, Yu-Ling
Wu, Yi-Ying
Kang, Chieh-Yi
Lin, Chun-Hong
Hsu, Pang-Hung
Lee, Gwo-Bin
Hsu, Keng-Fu
author_sort Lin, Chang-Ni
collection PubMed
description Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can specifically recognize serous carcinoma cells and tissues. Here, we aim to clarify the clinical role and possible molecular mechanisms of Tx-01 in OvCa. Immunostaining and statistical analysis were performed to detect the interaction of Tx-01 and heat shock protein 70/Notch1 intracellular domain (HSP70/NICD) in OvCa. The in vitro and in vivo experiments were carried out to demonstrate the potential mechanisms of Tx-01. Results show that Tx-01 reduced serous OvCa OVCAR3 cell migration and invasion and inhibited HSP70 nuclear translocation by interrupting the intracellular HSP70/NICD interaction. Furthermore, Tx-01 suppressed serous-type OVCAR3 cell tumor growth in vivo. Tx-01 acts as a prognostic factor through its interaction with membrane-bound HSP70 (mHSP70 that locates on the cell surface without direct interaction to NICD) on ascitic circulating tumor cells (CTCs) and is reported to be involved in natural killer (NK) cell recognition and activation. Our data demonstrated that Tx-01 interacted with HSP70 and showed therapeutic and prognostic effects in serous OvCa. Tx-01 might be a potential inhibitor for use in serous OvCa treatment.
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spelling pubmed-78687212021-02-19 An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer Lin, Chang-Ni Tsai, Yi-Cheng Hsu, Ching-Cheng Liang, Yu-Ling Wu, Yi-Ying Kang, Chieh-Yi Lin, Chun-Hong Hsu, Pang-Hung Lee, Gwo-Bin Hsu, Keng-Fu Mol Ther Nucleic Acids Original Article Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can specifically recognize serous carcinoma cells and tissues. Here, we aim to clarify the clinical role and possible molecular mechanisms of Tx-01 in OvCa. Immunostaining and statistical analysis were performed to detect the interaction of Tx-01 and heat shock protein 70/Notch1 intracellular domain (HSP70/NICD) in OvCa. The in vitro and in vivo experiments were carried out to demonstrate the potential mechanisms of Tx-01. Results show that Tx-01 reduced serous OvCa OVCAR3 cell migration and invasion and inhibited HSP70 nuclear translocation by interrupting the intracellular HSP70/NICD interaction. Furthermore, Tx-01 suppressed serous-type OVCAR3 cell tumor growth in vivo. Tx-01 acts as a prognostic factor through its interaction with membrane-bound HSP70 (mHSP70 that locates on the cell surface without direct interaction to NICD) on ascitic circulating tumor cells (CTCs) and is reported to be involved in natural killer (NK) cell recognition and activation. Our data demonstrated that Tx-01 interacted with HSP70 and showed therapeutic and prognostic effects in serous OvCa. Tx-01 might be a potential inhibitor for use in serous OvCa treatment. American Society of Gene & Cell Therapy 2021-01-05 /pmc/articles/PMC7868721/ /pubmed/33614227 http://dx.doi.org/10.1016/j.omtn.2020.12.025 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Lin, Chang-Ni
Tsai, Yi-Cheng
Hsu, Ching-Cheng
Liang, Yu-Ling
Wu, Yi-Ying
Kang, Chieh-Yi
Lin, Chun-Hong
Hsu, Pang-Hung
Lee, Gwo-Bin
Hsu, Keng-Fu
An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer
title An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer
title_full An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer
title_fullStr An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer
title_full_unstemmed An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer
title_short An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer
title_sort aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868721/
https://www.ncbi.nlm.nih.gov/pubmed/33614227
http://dx.doi.org/10.1016/j.omtn.2020.12.025
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