Vascular normalization induced by sinomenine hydrochloride results in suppressed mammary tumor growth and metastasis.
Solid tumor vasculature is characterized by structural and functional abnormality and results in a hostile tumor microenvironment that mediates several deleterious aspects of tumor behavior. Sinomenine is an alkaloid extracted from the Chinese medicinal plant, Sinomenium acutum, which has been utilized to treat rheumatism in China for over 2000 years. Though sinomenine has been demonstrated to mediate a wide range of pharmacological actions, few studies have focused on its effect on tumor vasculature. We showed here that intraperitoneally administration of 100 mg/kg sinomenine hydrochloride (SH, the hydrochloride chemical form of sinomenine) in two orthotopic mouse breast cancer models for 14 days, delayed mammary tumor growth and decreased metastasis by inducing vascular maturity and enhancing tumor perfusion, while improving chemotherapy and tumor immunity. The effects of SH on tumor vessels were caused in part by its capability to restore the balance between pro-angiogenic factor (bFGF) and anti-angiogenic factor (PF4). However 200 mg/kg SH didn't exhibit the similar inhibitory effect on tumor progression due to the immunosuppressive microenvironment caused by excessive vessel pruning, G-CSF upregulation, and GM-CSF downregulation. Altogether, our findings suggest that SH induced vasculature normalization contributes to its anti-tumor and anti-metastasis effect on breast cancer at certain dosage.
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Huimin
H
Zhang
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Yu
Y
Ren
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Xiaojiang
X
Tang
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Ke
K
Wang
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Yang
Y
Liu
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Li
L
Zhang
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Xiao
X
Li
Translational Medical center, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Peijun
P
Liu
Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Science, Beijing Normal University, Beijing 100875, P.R. China.
Changqi
C
Zhao
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, P.R. China.
Jianjun
J
He
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009019:Morphinans / Q000008:administration & dosage*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
D009019:Morphinans; C009271:sinomenine