Zhang Chun-Peng, Li Wei-Hua, Liu Jia-Ren, Li Guo-Dong, Zhang Hao-Peng, Wei Jiu-Feng, Chen Hong-Sheng, Zhao Jin-Lu, Wang Yun-Feng, Lv Qiang, Liu Ming
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Evid Based Complement Alternat Med. 2022 Sep 29;2022:9601020. doi: 10.1155/2022/9601020. eCollection 2022.
To further determine how BHE affected the growth of HCC cells, the proportion of each cell cycle phase was explored in HCC cells by flow cytometry. Blue honeysuckle ( L.) is a species of bush that grows in eastern Russia. Blue honeysuckle extract (BHE) is rich in bioactive phytochemicals which can inhibit the proliferation of tumor cells. The mechanism underlying the anticancer activity of BHE in primary liver cancer is poorly understood. The purpose of this study was to evaluate the growth inhibition mechanism of bioactive substances from blue honeysuckle on hepatocellular carcinoma (HCC) cells and to explore its protein and gene targets. The compounds in BHE were determined by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Cell counting kit-8 (CCK8) assay was used to evaluate the effects of BHE on HCC cell proliferation, and flow cytometry assay (FCA) was used to determine how BHE arrested the proportion of each cell cycle phase in HCC cells. Western blot (WB) was performed to determine the expression of cell cycle-related proteins in HCC cells treated with different concentrations of BHE. The xenograft tumor animal models were established by HCC cell implantation. The results showed that cyanidin-3-o-glucoside and cyanidin-3-o-sophoroside which are the main biologically active components were detected in BHE. BHE is highly effective in inhibiting the proliferation of HCC cells by arresting the HCC cell cycle in the G2/M phase. BHE also downregulated the expression of conventional or classical dendritic cells-2 (cDC2) and cyclin B1 by promoting the expression of myelin transcription factor 1 (MyT1) in HCC cells. The weight and volume of xenografts were significantly decreased in the BHE treated groups when compared to the control group. BHE increased the expression of MyT1 in xenograft tissues. These findings showed that blue honeysuckle extract inhibits proliferation and by downregulating the expression of cDC2 and cyclin B1 and upregulating the expression of MyT1 in HCC cells.
为进一步确定蓝靛果提取物（BHE）如何影响肝癌细胞的生长，通过流式细胞术研究了肝癌细胞中各细胞周期阶段的比例。蓝靛果是一种生长在俄罗斯东部的灌木。蓝靛果提取物富含生物活性植物化学物质，可抑制肿瘤细胞增殖。BHE在原发性肝癌中的抗癌活性机制尚不清楚。本研究的目的是评估蓝靛果生物活性物质对肝癌（HCC）细胞的生长抑制机制，并探索其蛋白质和基因靶点。通过高效液相色谱（HPLC）和液相色谱-质谱联用（LC-MS）测定BHE中的化合物。采用细胞计数试剂盒-8（CCK8）法评估BHE对肝癌细胞增殖的影响，流式细胞术（FCA）法测定BHE如何使肝癌细胞各细胞周期阶段的比例停滞。进行蛋白质免疫印迹（WB）以确定不同浓度BHE处理的肝癌细胞中细胞周期相关蛋白的表达。通过植入肝癌细胞建立异种移植肿瘤动物模型。结果表明，在BHE中检测到主要生物活性成分花青素-3-O-葡萄糖苷和花青素-3-O-槐糖苷。BHE通过使肝癌细胞周期停滞在G2/M期，对抑制肝癌细胞增殖非常有效。BHE还通过促进肝癌细胞中髓磷脂转录因子1（MyT1）的表达，下调传统或经典树突状细胞-2（cDC2）和细胞周期蛋白B1的表达。与对照组相比，BHE处理组的异种移植瘤重量和体积显著降低。BHE增加了异种移植组织中MyT1的表达。这些发现表明，蓝靛果提取物通过下调肝癌细胞中cDC2和细胞周期蛋白B1的表达以及上调MyT1的表达来抑制增殖。
