Comparative and mechanistic study of pharmacodynamic difference in anti-breast cancer activity between water and liquor extracts of Xiaojin Pills

体内 乳腺癌 癌症 医学 细胞凋亡 中医药 PI3K/AKT/mTOR通路 药理学 蛋白激酶B 癌症研究 传统医学 内科学 生物 病理 生物化学 生物技术 替代医学
作者
Huimin Liu,Bo Cao,Chunyu Li,Li Han,Hong Xu,Junzhi Lin,Dingkun Zhang,Runchun Xu
出处
期刊:Journal of Ethnopharmacology [Elsevier BV]
卷期号:291: 115104-115104 被引量:3
标识
DOI:10.1016/j.jep.2022.115104
摘要

Xiaojin Pills was first recorded during the Qing Dynasty and have a history of nearly 300 years. It is the first choice among Chinese patent medicines for the clinical treatment of diseases of the mammary glands in contemporary traditional Chinese medicine. It was also widely used in the treatment of breast cancer, lung cancer, thyroid cancer, and other malignant tumors. Its initial administration method was "taken orally after soaking with Chinese baijiu"; however, the method was changed to "taken orally with water" within the last 40 years. There is no scientific evidence for the difference in efficacy against breast cancer between the two methods of administration.In vitro and in vivo experiments were carried out to confirm the therapeutic advantages of the liquor extract of Xiaojin Pills to improve the efficacy against breast cancer, and the mechanism was explained in terms of metabolomics and molecular biology.In vitro, a cell counting kit-8 cell activity assay and flow cytometry were used to detect the activity and apoptosis of MCF-7 breast cancer cells. In vivo, pharmacodynamic evaluation was performed by constructing a heterotopic transplantation model of breast cancer in BALB/c-nu mice. TUNEL staining was used to observe the apoptosis of cells in tumor tissues. The expression of proteins associated with the phosphoinositide 3-kinase (PI3K)/Akt pathway in BALB/c-nu mice tissue was investigated by metabolomics analysis, immunohistochemistry and western blotting.CCK-8 assay showed that the IC50 of XJP-L for the inhibition of the activity of MCF-7 cells was less than that of XJP-W at different times. Flow cytometry assay suggested that the apoptosis rate in the XJP-L group was higher than that in the normal control group (p < 0.01). Animal experiment results indicated that both XJP-W group and XJP-L group reduced the volume and quality of the tumor after administration, and the reduction was more significant in the XJP-L group (p < 0.01). Metabolomics analysis results demonstrated that there are about 26 different metabolites have been screened in the serum metabolites between the liquor and water extract, mainly involved in glycerophospholipid, glutamic acid, aspartic acid, nitrogen and pyrimidine metabolism. In addition, immunohistochemistry and WB results showed that compared with the model group, the protein expression of PTEN, AKT, BAX and in tumor tissues of XJP-L and XJP-W groups both exhibited an upward trend, while the expression of BCL-2, p-PI3K and p-AKT exhibited a downward trend, which was much more obvious in XJP-L group.This study demonstrates that the liquor extract of Xiaojin Pills had a stronger anti-breast cancer effect than that of the water extract. The PI3K/Akt signaling pathway might play an important role in the mechanism of the liquor extract of Xiaojin Pills and thus improve the efficacy against breast cancer.
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