Aqueous extract of Chuan Xiong Rhizoma enhances inhibitory effect of temozolomide against brain metastasis of melanoma in mice
10.12122/j.issn.1673-4254.2024.06.09
- VernacularTitle:川芎增强替莫唑胺对小鼠脑转移黑色素瘤脑的抑制作用
- Author:
Qian ZHAO
1
;
Zhen ZHANG
;
Xingqi ZHOU
;
Xiangyu RONG
;
Xuerou LIU
;
Xinli ZHAO
;
Haojie WANG
;
Jinlong PANG
;
Shanshan LI
;
Xian LI
Author Information
1. 蚌埠医科大学药学院,安徽 蚌埠 233030
- Keywords:
Chuan Xiong Rhizoma;
Melanoma;
temozolomide;
blood-brain barrier;
brain metastases
- From:
Journal of Southern Medical University
2024;44(6):1088-1097
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of the aqueous extract of Chuan Xiong Rhizoma(CR)on brain metastasis of melanoma B16F10 cells in mice.Methods C57BL/6J mouse models of brain metastasis of melanoma were established by ultrasound-guided intraventricular injection of Luc-labeled B16F10 cells,and brain tumor growth was monitored by in vivo imaging.The mouse models were then randomized for daily gavage of saline or aqueous extract of CR(equivalent crude drug concentration of 1 mg/g).Behavioral tests were used to evaluate the neuroprotective effects of CR in the tumor-bearing mice,and the changes in proteins associated with blood-brain barrier integrity,neuronal cell proliferation and apoptosis,and microglial cell apoptosis and activation were observed using immunofluorescence assay.The efficacy of CR combined with temozolomide(25 mg/kg)against brain metastases of B16F10 cells was observed by in vivo imaging.Results CR-treated mouse models did not show obvious progression of brain metastases and had a reduced rate of body weight loss and lowered protein expressions of ZO-1,claudin-5,occludin,P-gp,TNF-α,AQP4 and PDGFRβ.In the behavioral tests,the CR-treated mice showed prolonged stay on the wooden stick with a shortened time of sticky stick removal.Immunofluorescence assay showed increased proliferation and decreased apoptosis of neuronal cells and microglia in CR-treated mice.CR treatment significantly increased the levels of CD86,CD206,IL-4 and IL-10 and decreased the levels of CD163 and IL-1β in the microenvironment of brain metastases.The mice receiving combined treatments with CR and temozolomide showed significantly lower intensity of fluorescent signals in the brain than those treated with temozolomide alone.Conclusion CR does not promote brain metastasis of melanoma while inducing opening of the blood-brain barrier,and its combined use with TMZ results in enhanced inhibition against brain metastasis of melanoma B16F10 cells in mice.
