Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism

Ying Qi; Xin-Jie Wu; Jing-Bin Shi; Xiao-Wei Shi; Na Zhao; Yang Xiong; Li-Pei Wang

doi:10.1007/s11655-023-3555-x

Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism

Chin J Integr Med. 2023 Nov 6. doi: 10.1007/s11655-023-3555-x. Online ahead of print.

Authors

Ying Qi^{1

2}, Xin-Jie Wu^{1

2}, Jing-Bin Shi³, Xiao-Wei Shi³, Na Zhao³, Yang Xiong³, Li-Pei Wang^{4

5}

Affiliations

¹ School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 311121, China.
² Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, 311121, China.
³ Zhejiang Chinese Medical University, Hangzhou, 310053, China.
⁴ School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 311121, China. Wanglipei_zju@163.com.
⁵ Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, 311121, China. Wanglipei_zju@163.com.

PMID: 37930511
DOI: 10.1007/s11655-023-3555-x

Abstract

Objective: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism.

Methods: 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.

Results: 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.

Conclusion: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

Keywords: Janus kinase 2-signal transducer and activator of transcription 3; Sanhuang Xiexin Decoction; epithelial-mesenchymal transition; lipid metabolism; triple-negative breast cancer.