Ann Transl Med. 2021 Sep;9(17):1389. doi: 10.21037/atm-21-4199.
[No title available]
Annals of translational medicine
En-Qi Qiao, Hong-Jian Yang, Xing-Fei Yu, Li-Jie Gong, Xi-Ping Zhang, Dao-Bao Chen
Affiliations
Affiliations
- Department of Breast Tumor Surgery, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.
PMID: 34733941
PMCID: PMC8506551 DOI: 10.21037/atm-21-4199
Abstract
BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by its aggressiveness and poor prognosis. Docetaxel is the common chemotherapeutic drug used in the treatment of TNBC. However, resistance to docetaxel has limited the effectiveness of TNBC treatment. Petroleum ether extracts of
METHODS: A docetaxel-resistant MDA-MB-231 (MDA-MB-231/docetaxel) cell line was established, and Cell Counting Kit-8 (CCK-8), quantitative real-time PCR (qRT-PCR), and western blotting assays were used to evaluate the effect of docetaxel resistance in MDA-MB-231 cells. Next, CCK-8 was also performed to detect the effect of docetaxel or the combination treatment of docetaxel and PECZ on the proliferation of MDA-MB-231/docetaxel cells. Thereafter, MDA-MB-231/docetaxel cells were subcutaneously injected into nude mice to induce a TNBC xenograft model, and the mice were divided into a model group, docetaxel group, PECZ group, and combination of docetaxel and PECZ group. Subsequently, hematoxylin and eosin (HE) staining, immunohistochemical, qRT-PCR, and western blotting were used to estimate the effect of pre-treatment with PECZ on docetaxel tolerance reversal.
RESULTS: PECZ significantly inhibited the expression of pregnane X receptor (PXR), multidrug resistance 1 (MDR1), breast cancer resistance protein (BCRP), and cytochrome P-450 (CYP3A4) in MDA-MB-231/docetaxel cells. Only higher concentrations of docetaxel could inhibit the viability of MDA-MB-231/docetaxel cells. When pre-treated with PECZ, lower concentrations of docetaxel could significantly inhibit cell viability. Meanwhile, combination treatment also reduced the tumor volume, ameliorated the pathological change of tumor tissues, and down-regulated the expressions of PXR, MDR1, BCRP, and CYP3A4 (according to HE staining, immunohistochemical, qRT-PCR and western blotting results
CONCLUSIONS: Our research showed that PECZ reversed docetaxel resistance in TNBC by PXR both
2021 Annals of Translational Medicine. All rights reserved.
Keywords: MDA-MB-231; Triple-negative breast cancer (TNBC); docetaxel-resistant; rhizoma zedoaria petroleum ether extract
Conflict of interest statement
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4199). The authors have no conflicts of interest to declare.
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