三黄泻心汤通过调节 JAK2-STAT3 和脂质代谢改善 TNBC。
Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism.
发表日期:2023 Nov 06
作者:
Ying Qi, Xin-Jie Wu, Jing-Bin Shi, Xiao-Wei Shi, Na Zhao, Yang Xiong, Li-Pei Wang
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
目的探讨三黄泻心汤(SXD)对小鼠三阴性乳腺癌(TNBC)的治疗作用及其机制。采用高效液相色谱(HPLC)对SXD进行定量和定性。 15只雌性BALB/c小鼠右侧腹下皮下接种3×105个4T1-Luc细胞,建立TNBC小鼠模型。所有小鼠随机分为3组,包括磷酸盐缓冲液(PBS)组、SXD组和阿霉素(DOX)组(阳性药物组)。此外,肿瘤生长、病理变化、血脂谱、Janus激酶2(JAK2)信号转导子和转录激活子3(STAT3)信号通路的表达及其关键靶标,包括炎症因子、细胞周期和上皮间质转化(EMT) )标记进行了研究。此外,还在小鼠体内评价了SXD的生物安全性。SXD中均含有大黄酸、黄连碱、盐酸小檗碱和黄芩苷,这4种成分的浓度分别为0.57、2.61、2.93和46.04 mg/g。小鼠实验表明,SXD能显着抑制肿瘤的发展,降低肿瘤细胞密度(P<0.01)。血脂分析和油红O染色均显示差异,SXD组血清脂联素和HDL-C水平高于PBS组和DOX组,TC和LDL-C水平低于PBS组和DOX组(P<0.05或P<0.01) ), 分别。 SXD 还降低磷酸-JAK2 (p-JAK2)、磷酸-STAT3 (p-STAT3) 表达及其下游因子的水平,其中主要包括炎症细胞因子、EMT 标志物、肿瘤细胞的 S 期和血管内皮生长因子 (VEGF)分别表达(P<0.05 或 P<0.01)。 SXD 的生物安全性评估显示对小鼠的毒性较低。SXD 可以通过抑制 JAK2-STAT3 磷酸化来抑制 TNBC,而 JAK2-STAT3 磷酸化可能与脂质代谢的调节有关。© 2023。中华中西医结合杂志和 Springer-Verlag GmbH 德国,隶属于施普林格自然集团。
To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism.The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice.Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice.SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.