TY - JOUR
T1 - Effects of Jaeumkanghwa-tang on tamoxifen responsiveness in preclinical ER+ breast cancer model
AU - Andrade, Fabia De Oliveira
AU - Yu, Wei
AU - Zhang, Xiyuan
AU - Carney, Elissa
AU - Hu, Rong
AU - Clarke, Robert
AU - FitzGerald, Kevin
AU - Hilakivi-Clarke, Leena
N1 - Publisher Copyright:
© 2019 The authors Published by Bioscientifica Ltd.
PY - 2019/3
Y1 - 2019/3
N2 - Resistance to endocrine therapy remains a clinical challenge in the treatment of estrogen receptor-positive (ER+) breast cancer. We investigated if adding a traditional Asian herbal mixture consisting of 12 herbs, called Jaeumkanghwa-tang (JEKHT), to tamoxifen (TAM) therapy might prevent resistance and recurrence in the ER+ breast cancer model of 7,12-dimethylbenz[a]anthracene (DMBA)-exposed Sprague–Dawley rats. Rats were divided into four groups treated as follows: 15 mg/kg TAM administered via diet as TAM citrate (TAM only); 500 mg/kg JEKHT administered via drinking water (JEKHT only group); TAM + JEKHT and no treatment control group. The study was replicated using two different batches of JEKHT. In both studies, a significantly higher proportion of ER+ mammary tumors responded to TAM if animals also were treated with JEKHT (experiment 1: 47% vs 65%, P = 0.015; experiment 2: 43% vs 77%, P < 0.001). The risk of local recurrence also was reduced (31% vs 12%, P = 0.002). JEKHT alone was mostly ineffective. In addition, JEKHT prevented the development of premalignant endometrial lesions in TAM-treated rats (20% in TAM only vs 0% in TAM + JEKHT). Co-treatment of antiestrogen-resistant LCC9 human breast cancer cells with 1.6 mg/mL JEKHT reversed their TAM resistance in dose–response studies in vitro. Several traditional herbal medicine preparations can exhibit anti-inflammatory properties and may increase anti-tumor immune activities in the tumor microenvironment. In the tumors of rats treated with both JEKHT and TAM, expression of Il-6 (P = 0.03), Foxp3/T regulatory cell (Treg) marker (P = 0.033) and Tgfβ1 that activates Tregs (P < 0.001) were significantly downregulated compared with TAM only group. These findings indicate that JEKHT may prevent TAM-induced evasion of tumor immune responses.
AB - Resistance to endocrine therapy remains a clinical challenge in the treatment of estrogen receptor-positive (ER+) breast cancer. We investigated if adding a traditional Asian herbal mixture consisting of 12 herbs, called Jaeumkanghwa-tang (JEKHT), to tamoxifen (TAM) therapy might prevent resistance and recurrence in the ER+ breast cancer model of 7,12-dimethylbenz[a]anthracene (DMBA)-exposed Sprague–Dawley rats. Rats were divided into four groups treated as follows: 15 mg/kg TAM administered via diet as TAM citrate (TAM only); 500 mg/kg JEKHT administered via drinking water (JEKHT only group); TAM + JEKHT and no treatment control group. The study was replicated using two different batches of JEKHT. In both studies, a significantly higher proportion of ER+ mammary tumors responded to TAM if animals also were treated with JEKHT (experiment 1: 47% vs 65%, P = 0.015; experiment 2: 43% vs 77%, P < 0.001). The risk of local recurrence also was reduced (31% vs 12%, P = 0.002). JEKHT alone was mostly ineffective. In addition, JEKHT prevented the development of premalignant endometrial lesions in TAM-treated rats (20% in TAM only vs 0% in TAM + JEKHT). Co-treatment of antiestrogen-resistant LCC9 human breast cancer cells with 1.6 mg/mL JEKHT reversed their TAM resistance in dose–response studies in vitro. Several traditional herbal medicine preparations can exhibit anti-inflammatory properties and may increase anti-tumor immune activities in the tumor microenvironment. In the tumors of rats treated with both JEKHT and TAM, expression of Il-6 (P = 0.03), Foxp3/T regulatory cell (Treg) marker (P = 0.033) and Tgfβ1 that activates Tregs (P < 0.001) were significantly downregulated compared with TAM only group. These findings indicate that JEKHT may prevent TAM-induced evasion of tumor immune responses.
KW - Breast cancer
KW - Endometrial atypical hyperplasia
KW - Jaeumkanghwa-tang
KW - Preclinical
KW - Tamoxifen
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UR - http://www.scopus.com/inward/citedby.url?scp=85061380860&partnerID=8YFLogxK
U2 - 10.1530/ERC-18-0393
DO - 10.1530/ERC-18-0393
M3 - Article
C2 - 30640711
AN - SCOPUS:85061380860
SN - 1351-0088
VL - 26
SP - 339
EP - 353
JO - Endocrine-related cancer
JF - Endocrine-related cancer
IS - 3
ER -