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超临界提取物通过增加 AMPK 和 MAPKs 介导的细胞凋亡和细胞周期阻滞抑制结直肠癌细胞的肺转移。

Supercritical Extract of Inhibits Lung Metastasis in Colorectal Cancer Cells by Increasing AMPK and MAPKs-Mediated Apoptosis and Cell Cycle Arrest.

机构信息

Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, Korea.

Department of Oriental Medicine Resources, Jeonbuk National University, 79 Gobong-ro, Iksan 54596, Jeonbuk, Korea.

出版信息

Nutrients. 2022 Oct 28;14(21):4548. doi: 10.3390/nu14214548.

Abstract

Colorectal cancer (CRC) is one of the diseases with the highest rates of prevalence and mortality despite therapeutic methods in the world. In particular, there are not enough methods to treat metastasis of CRC cells to distant organs. Linne () is a popular medicinal plant used by humans to treat many diseases. Recently, extracts of have shown diverse pharmacological effects as a result of choosing different extraction methods. In this study, we performed experiments to confirm the inhibitory effect and related mechanisms of supercritical extract of on metastatic CRC cells. The effect of SEC on the viability of CRC cell lines, CT26 and HCT116, was determined using CCK reagent. Flow cytometry was performed to confirm whether SEC can promote cell cycle arrest and apoptosis. Additionally, SEC reduced proliferation of CT26 and HCT116 cells without causing toxicity to normal colon cell line CCD-18Co cells. SEC treatment reduced colony formation in both CRC cell lines, promoted G0/G1 phase arrest and apoptosis in CT26 and HCT116 cells through AMPK activation and MAPKs such as ERK, JNK, and p38 inactivation. Moreover, oral administration of SEC decreased pulmonary metastasis of CT26 cells. Our research demonstrates the inhibitory effect of SEC on CRC cell proliferation and metastasis. Thus, SEC might have therapeutic potential for CRC treatment.

摘要

结直肠癌(CRC)是世界范围内发病率和死亡率最高的疾病之一。特别是,对于 CRC 细胞向远处器官转移的治疗方法还不够。 Linné(林奈)是一种常用的药用植物,人类用它来治疗许多疾病。最近,由于选择了不同的提取方法, 的提取物表现出了多样化的药理作用。在这项研究中,我们进行了实验,以确认超临界提取物对转移性 CRC 细胞的抑制作用及相关机制。使用 CCK 试剂测定 SEC 对 CRC 细胞系 CT26 和 HCT116 活力的影响。通过流式细胞术证实 SEC 是否能促进细胞周期停滞和细胞凋亡。此外,SEC 处理不会对正常结肠细胞系 CCD-18Co 细胞造成毒性,但能抑制 CT26 和 HCT116 细胞的增殖。SEC 处理能促进 CT26 和 HCT116 细胞中 AMPK 的激活,抑制 ERK、JNK 和 p38 等 MAPKs 的活性,从而导致 G0/G1 期阻滞和细胞凋亡,减少两种 CRC 细胞系的集落形成。此外,SEC 的口服给药能降低 CT26 细胞的肺转移。我们的研究表明 SEC 对 CRC 细胞增殖和转移有抑制作用。因此,SEC 可能具有治疗 CRC 的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e3/9657598/f5e41c6fc678/nutrients-14-04548-g001.jpg

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