Cargando…

SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer

Although many anticancer drugs have been developed for triple-negative breast cancer (TNBC) treatment, there are no obvious therapies. Moreover, the combination of epidermal growth factor receptor- (EGFR-) targeted therapeutics and classical chemotherapeutic drugs has been assessed in clinical trial...

Descripción completa

Detalles Bibliográficos
Autores principales: Choi, Yu-Jeong, Lee, Kangwook, Yoon, Ji-Hye, Cho, Sung-Gook, Kim, Yun-Gyeong, Jeong, Miso, Hwang, Hyun-Ha, Lee, Seo Yeon, Jung, Se-Eun, Ko, Seong-Gyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098291/
https://www.ncbi.nlm.nih.gov/pubmed/35572726
http://dx.doi.org/10.1155/2022/3647900
_version_ 1784706349124288512
author Choi, Yu-Jeong
Lee, Kangwook
Yoon, Ji-Hye
Cho, Sung-Gook
Kim, Yun-Gyeong
Jeong, Miso
Hwang, Hyun-Ha
Lee, Seo Yeon
Jung, Se-Eun
Ko, Seong-Gyu
author_facet Choi, Yu-Jeong
Lee, Kangwook
Yoon, Ji-Hye
Cho, Sung-Gook
Kim, Yun-Gyeong
Jeong, Miso
Hwang, Hyun-Ha
Lee, Seo Yeon
Jung, Se-Eun
Ko, Seong-Gyu
author_sort Choi, Yu-Jeong
collection PubMed
description Although many anticancer drugs have been developed for triple-negative breast cancer (TNBC) treatment, there are no obvious therapies. Moreover, the combination of epidermal growth factor receptor- (EGFR-) targeted therapeutics and classical chemotherapeutic drugs has been assessed in clinical trials for TNBC treatment, but those are not yet approved. Our serial studies for newly developed herbal medicine named SH003 provide evidence of its broad effectiveness in various cancers, especially on TNBC. The current study demonstrates a synergic effect of combinatorial treatment of SH003 and docetaxel (DTX) by targeting EGFR activation. The combinatorial treatment reduced the viability of both BT-20 and MDA-MB-231 TNBC cells, displaying the synergism. The combination of SH003 and DTX also caused the synergistic effect on apoptosis. Mechanistically, the cotreatment of SH003 and DTX inhibited phosphorylation of EGFR and AKT in both BT-20 and MDA-MB-231 cells. Moreover, our xenograft mouse tumor growth assays showed the inhibitory effect of the combinatorial treatment with no effect on body weight. Our immunohistochemistry confirmed its inhibition of EGFR phosphorylation in vivo. Collectively, combinatorial treatment of SH003 and DTX has a synergistic anticancer effect at a relatively low concentration by targeting EGFR in TNBC, indicating safety and efficacy of SH003 as adjuvant combination therapy with docetaxel. Thus, it is worth testing the combinatorial effect in clinics for treating TNBC.
format Online
Article
Text
id pubmed-9098291
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-90982912022-05-13 SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer Choi, Yu-Jeong Lee, Kangwook Yoon, Ji-Hye Cho, Sung-Gook Kim, Yun-Gyeong Jeong, Miso Hwang, Hyun-Ha Lee, Seo Yeon Jung, Se-Eun Ko, Seong-Gyu Biomed Res Int Research Article Although many anticancer drugs have been developed for triple-negative breast cancer (TNBC) treatment, there are no obvious therapies. Moreover, the combination of epidermal growth factor receptor- (EGFR-) targeted therapeutics and classical chemotherapeutic drugs has been assessed in clinical trials for TNBC treatment, but those are not yet approved. Our serial studies for newly developed herbal medicine named SH003 provide evidence of its broad effectiveness in various cancers, especially on TNBC. The current study demonstrates a synergic effect of combinatorial treatment of SH003 and docetaxel (DTX) by targeting EGFR activation. The combinatorial treatment reduced the viability of both BT-20 and MDA-MB-231 TNBC cells, displaying the synergism. The combination of SH003 and DTX also caused the synergistic effect on apoptosis. Mechanistically, the cotreatment of SH003 and DTX inhibited phosphorylation of EGFR and AKT in both BT-20 and MDA-MB-231 cells. Moreover, our xenograft mouse tumor growth assays showed the inhibitory effect of the combinatorial treatment with no effect on body weight. Our immunohistochemistry confirmed its inhibition of EGFR phosphorylation in vivo. Collectively, combinatorial treatment of SH003 and DTX has a synergistic anticancer effect at a relatively low concentration by targeting EGFR in TNBC, indicating safety and efficacy of SH003 as adjuvant combination therapy with docetaxel. Thus, it is worth testing the combinatorial effect in clinics for treating TNBC. Hindawi 2022-05-05 /pmc/articles/PMC9098291/ /pubmed/35572726 http://dx.doi.org/10.1155/2022/3647900 Text en Copyright © 2022 Yu-Jeong Choi et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Choi, Yu-Jeong
Lee, Kangwook
Yoon, Ji-Hye
Cho, Sung-Gook
Kim, Yun-Gyeong
Jeong, Miso
Hwang, Hyun-Ha
Lee, Seo Yeon
Jung, Se-Eun
Ko, Seong-Gyu
SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer
title SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer
title_full SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer
title_fullStr SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer
title_full_unstemmed SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer
title_short SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer
title_sort sh003 and docetaxel show synergistic anticancer effects by inhibiting egfr activation in triple-negative breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098291/
https://www.ncbi.nlm.nih.gov/pubmed/35572726
http://dx.doi.org/10.1155/2022/3647900
work_keys_str_mv AT choiyujeong sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT leekangwook sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT yoonjihye sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT chosunggook sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT kimyungyeong sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT jeongmiso sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT hwanghyunha sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT leeseoyeon sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT jungseeun sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer
AT koseonggyu sh003anddocetaxelshowsynergisticanticancereffectsbyinhibitingegfractivationintriplenegativebreastcancer