Sinomenine hydrochloride suppresses breast cancer growth by inhibiting bFGF-induced angiogenesis / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To investigate the effect of sinomenine hydrochloride （SH） on angiogenesis and the underlying mechanism in breast cancer. 【Methods】 The 4T1 orthotopic tumor model of breast cancer was utilized， and mice were treated with different dosage of SH to investigate the effect of SH on tumor growth. IHC staining of CD31 was used to evaluate angiogenesis within tumors under different treatment. ELISA was performed to measure the bFGF level within tumor extracellular fluid （TEF） and tumor cells to analyze the effect of SH on bFGF secretion and production. RT-qPCR was utilized to evaluate the effect of SH on the mRNA expression of bFGF in tumor cells. Kaplan-Meier Plotter was analyzed online to investigate the relationship between bFGF expression and the survival of patients with breast cancer. 【Results】 SH at 100 mg/kg could inhibit 4T1 orthotopic tumor growth compared with saline （P<0.05）， but SH showed little cytotoxicity in vitro under the tested concentrations. SH at 100 mg/kg suppressed the vessel area compared with saline （P<0.01）， and the concentration of angiogenic factor bFGF in TEF and tumor cells was decreased by SH treatment （P<0.05）， while the mRNA expression of bFGF in tumor cells was also downregulated by SH treatment （P<0.05）. Kaplan-Meier Plotter online analysis showed that elevated mRNA expression of bFGF in the primary tumor was associated with poorer OS， RFS and DMFS in patients with breast cancer （P<0.01）. 【Conclusion】 SH inhibits breast cancer growth by suppressing bFGF-induced angiogenesis， which enriches the pharmacological effects of this traditional Chinese medicine.