Berbamine dihydrochloride suppresses the progression of colorectal cancer via RTKs/Akt axis

作者全名："Liu, Lu; Liang, Dan; Zheng, Qiao; Zhao, Maoyuan; Lv, RuiTing; Tang, Jianyuan; Chen, Nianzhi"

作者地址："[Liu, Lu; Chen, Nianzhi] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing, Peoples R China; [Liu, Lu; Liang, Dan; Zheng, Qiao; Zhao, Maoyuan; Tang, Jianyuan] Hosp Chengdu Univ Tradit Chinese Med, TCM Regulating Metab Dis Key Lab Sichuan Prov, Chengdu, Peoples R China; [Lv, RuiTing] Hosp Chengdu Univ Tradit Chinese Med, Dept Oncol, Chengdu, Peoples R China"

通信作者："Chen, NZ (通讯作者)，Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing, Peoples R China.; Tang, JY (通讯作者)，Hosp Chengdu Univ Tradit Chinese Med, TCM Regulating Metab Dis Key Lab Sichuan Prov, Chengdu, Peoples R China."

来源：JOURNAL OF ETHNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000898695900001

JCR分区：Q1

影响因子：5.4

年份：2023

卷号：303

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Berbamine dihydrochloride; Colorectal cancer; RTKs; Akt pathway

摘要："Ethnopharmacological relevance: Berberis amurensis Rupr. is used to treat cancer as a traditional herbal medicine. Berbamine (BBM) is a natural bisbenzylisoquinoline alkaloid extracted from Berberis amurensis which possesses multiple pharmacological activity including anticancer.Aim of the study: To investigate the influence of BBM on the progression of colorectal cancer (CRC) and further explore the underlying mechanism of BBM based on the RTKs/Akt signaling pathway.Materials and methods: In vitro, cell viability and colony formation were conducted to detect BBM inhibitory of CRC cell lines. Transwell was detected the ability of migration and invasion by BBM. Apoptosis detection assay, cell cycle assay and the measurement of ROS were detected to confirm the inductive effect of cell apoptosis. RT-qPCR and Western blot to clarify the specific mechanism of anticancer. Finally, we conducted HE staining, Ki67, Tunnel and immunochemistry were confirmed the anti-colorectal cancer activity of BBM from vivo study.Results: We found that BBM could inhibit CRC cell lines growth. Moreover, BBM presented an inhibitory effect the ability of migration and invasion in CRC cells. Furthermore, the occurrence of apoptosis was involved in the anti-colorectal cancer role of BBM. BBM also triggered ROS accumulation in CRC cells that might be a key factor for the inductive effect of BBM in cell apoptosis. Cell cycle assay revealed that BBM induced the arrest of G1-S phase and increased the p21 levels but decreased CyclinE1, CyclinE2, CDK6, CyclinD1. RT-qPCR manifested that the down-regulation effect of BBM on AKT1, EGFR, PDGFR alpha and FGFR4 genes. The results also showed that BBM could decreased the expression levels of phosphor-AKT, PDGFR alpha, PDGFR beta, EGFR, FGFR3 and FGFR4 which belong to RTKs family. Consistently, BBM remarkably suppressed tumor xenograft growth in nude mice.Conclusion: Taken together, all the results as presented above suggest that BBM as a novel multitargeted receptor tyrosine kinase inhibitor plays a crucial role in the inhibitory effect of CRC and may be a promising therapeutic agent for the CRC in clinic."

基金机构：National Nature Science Foundation of China [82074397]; Hundred Talents Program of the Hospital of Chengdu University of Traditional Chinese Medicine [20-L01]; Central Government Guides Local Science and Technology development Projects of Sichuan Provincial Science and Technology Department [2021ZYD0107]

基金资助正文："This work was supported by the National Nature Science Foundation of China (No.82074397) , Hundred Talents Program of the Hospital of Chengdu University of Traditional Chinese Medicine (No.20-L01) , The Central Government Guides Local Science and Technology development Projects of Sichuan Provincial Science and Technology Department (No. 2021ZYD0107) ."