提取物通过抑制 SW480 人结肠癌细胞中 AKT 的激活诱导细胞凋亡。

extract induces apoptosis by inhibiting the activation of AKT in SW480 human colon cancer cells.

机构信息

Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, People's Republic of China.

Sino-Canada Joint Zebrafish Lab for Chinese Herbal Drug Screening, Guangxi University of Chinese Medicine, Nanning, People's Republic of China.

出版信息

Pharm Biol. 2022 Dec;60(1):915-930. doi: 10.1080/13880209.2022.2063340.

DOI:10.1080/13880209.2022.2063340

PMID:35587342

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9122364/

Abstract

CONTEXT

Markgr. (Gnetaceae) is used to treat rheumatic arthralgia and bruises in the clinic.

OBJECTIVE

To exam the activity and mechanism of extract (GME) against colon cancer cells SW480.

MATERIALS AND METHODS

The anti-proliferative activity of GME (0-120 μg/mL) on SW480 cells was determined using MTS assay at 24, 48, and 72 h. The activity of GME (0-120 μg/mL) on SW480 cells was investigated using flow cytometry and western blotting analysis. The activity of GME was evaluated using xenograft tumour model of zebrafish and nude mice. The chemical composition of GME was detected by using HPLC-MS/MS.

RESULTS

The IC value SW480 cells viability by GME were 126.50, 78.25, and 50.77 μg/mL, respectively, for 24, 48, and 72 h. The experiments showed that apoptotic cells and G2/M phase cells increased from 20.81 to 61.53% ( < 0.01) and 25.76 to 34.93% with 120 μg/mL GME, respectively. GME also down-regulated the protein expression of P-AKT, P-GSK-3β, P-PDK1, P-c-Raf, caspase-3, and Bcl-2, and up-regulated the expression cleaved caspase-3, cleaved PARP, and Bax. study found that GME can significantly inhibit the growth and migration of SW480 cells in xenograft zebrafish. GME reduced the nude mice tumour weight to approximately 32.19% at 28 mg/kg/day and to 53.17% ( < 0.01) at 56 mg/kg/day. Forty-two compounds were identified from the GME.

DISCUSSION AND CONCLUSIONS

GME has a significant antitumor effect on colon cancer cells SW480, and it has the potential to be developed as an anticancer agent.

摘要

背景

黄杞（Gnetaceae）在临床上用于治疗风湿性关节炎和跌打损伤。

目的

研究提取物（GME）对结肠癌细胞 SW480 的活性和作用机制。

材料和方法

采用 MTS 法在 24、48 和 72 h 时测定 GME（0-120 μg/mL）对 SW480 细胞的增殖抑制活性。采用流式细胞术和 Western blot 分析研究 GME（0-120 μg/mL）对 SW480 细胞的作用。采用斑马鱼和裸鼠异种移植肿瘤模型评价 GME 的作用。采用 HPLC-MS/MS 检测 GME 的化学成分。

结果

GME 对 SW480 细胞活力的 IC 值分别为 126.50、78.25 和 50.77 μg/mL，作用 24、48 和 72 h。实验表明，120 μg/mL GME 可使凋亡细胞和 G2/M 期细胞分别从 20.81%增加到 61.53%（ < 0.01）和从 25.76%增加到 34.93%。GME 还下调了 P-AKT、P-GSK-3β、P-PDK1、P-c-Raf、caspase-3 和 Bcl-2 的蛋白表达，上调了 cleaved caspase-3、cleaved PARP 和 Bax 的表达。研究发现，GME 能显著抑制 SW480 细胞在异种移植斑马鱼中的生长和迁移。GME 使 28 mg/kg/d 组裸鼠肿瘤重量减少至约 32.19%，56 mg/kg/d 组减少至 53.17%（ < 0.01）。从 GME 中鉴定出 42 种化合物。