Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Choi YJ

PROVIDER: S-EPMC9098291 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Choi Yu-Jeong YJ Lee Kangwook K Yoon Ji-Hye JH Cho Sung-Gook SG Kim Yun-Gyeong YG Jeong Miso M Hwang Hyun-Ha HH Lee Seo Yeon SY Jung Se-Eun SE Ko Seong-Gyu SG

BioMed research international 20220505

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 T ...[more]

PMID: 35572726

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Project description:Exosomes are carriers of intercellular information that regulate the tumor microenvironment, and they have an essential role in drug resistance through various mechanisms such as transporting RNA molecules and proteins. Nevertheless, their effects on gemcitabine resistance in triple-negative breast cancer (TNBC) are unclear. In the present study, we examined the effects of exosomes on TNBC cell viability, colony formation, apoptosis, and annexin A6 (ANXA6)/EGFR expression. We addressed their roles in gemcitabine resistance and the underlying mechanism. Our results revealed that exosomes derived from resistant cancer cells improved cell viability and colony formation and inhibited apoptosis in sensitive cancer cells. The underlying mechanism included the transfer of exosomal ANXA6 from resistant cancer cells to sensitive cancer cells. Isobaric peptide labeling-liquid chromatography-tandem mass spectrometry and western blotting revealed that ANXA6 was upregulated in resistant cancer cells and their derived exosomes. Sensitive cancer cells exhibited resistance with increased viability and colony formation and decreased apoptosis when ANXA6 was stably overexpressed. On the contrary, knockdown ANXA6 restored the sensitivity of cells to gemcitabine. Co-immunoprecipitation expression and GST pulldown assay demonstrated that exosomal ANXA6 and EGFR could interact with each other and exosomal ANXA6 was associated with the suppression of EGFR ubiquitination and downregulation. While adding lapatinib reversed gemcitabine resistance induced by exosomal ANXA6. Moreover, ANXA6 and EGFR protein expression was correlated in TNBC tissues, and exosomal ANXA6 levels at baseline were lower in patients with highly sensitive TNBC than those with resistant TNBC when treated with first-line gemcitabine-based chemotherapy. In conclusion, resistant cancer cell-derived exosomes induced gemcitabine resistance via exosomal ANXA6, which was associated with the inhibition of EGFR ubiquitination and degradation. Exosomal ANXA6 levels in the serum of patients with TNBC might be predictive of the response to gemcitabine-based chemotherapy.

Dataset Information

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

Publications

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

Similar Datasets

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