Objective:

2

To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triplenegative breast cancer (TNBC) in mice and its underlying mechanism.

Methods:

2

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 3×10

5

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 evaluat

ed in mice.

Results:

2

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:

2

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