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Main Authors: Zhang, Yunfang, Wu, Wei, Shi, Yan, Huang, Yuehong, Dai, Ting, Ke, Lina, Chen, Lizhu, Chen, Mingliang, Wang, Qin
Format: Artículo científico
Language:en
Published: International journal of molecular sciences 2024
Subjects:
Online Access:https://pubmed.ncbi.nlm.nih.gov/39769205/
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author Zhang, Yunfang
Wu, Wei
Shi, Yan
Huang, Yuehong
Dai, Ting
Ke, Lina
Chen, Lizhu
Chen, Mingliang
Wang, Qin
author_facet Zhang, Yunfang
Wu, Wei
Shi, Yan
Huang, Yuehong
Dai, Ting
Ke, Lina
Chen, Lizhu
Chen, Mingliang
Wang, Qin
Zhang, Yunfang
Wu, Wei
Shi, Yan
Huang, Yuehong
Dai, Ting
Ke, Lina
Chen, Lizhu
Chen, Mingliang
Wang, Qin
collection PubMed - marine biology
contents Apoptosis-Inducing and Proliferation-Inhibiting Effects of Doramectin on Mz-ChA-1 Human Cholangiocarcinoma Cells. Zhang, Yunfang Wu, Wei Shi, Yan Huang, Yuehong Dai, Ting Ke, Lina Chen, Lizhu Chen, Mingliang Wang, Qin Humans Cholangiocarcinoma Cell Proliferation Apoptosis Ivermectin Cell Line, Tumor Bile Duct Neoplasms Cell Movement Reactive Oxygen Species Antineoplastic Agents Gene Expression Regulation, Neoplastic Cholangiocarcinoma is a malignant tumor that emerges in the intrahepatic or extrahepatic bile ducts. Doramectin (DOR), a third-generation derivative of avermectins (AVMs), is renowned for its low toxicity and high efficiency. However, no research has hitherto focused on the anti-cholangiocarcinoma effects of these drugs. In this study, we undertook a preliminary exploration of the mechanism through which DOR inhibits the viability of human cholangiocarcinoma cells (Mz-ChA-1) via transcriptome analysis and molecular validation at the cellular level. The results indicated that DOR could suppress the growth and proliferation of Mz-ChA-1 cells in a dose-dependent manner. Moreover, it significantly diminished their migration and invasion abilities. Cell cycle analysis disclosed arrest in the G1 phase, accompanied by an increase in p21 expression and a decrease in the levels of the cyclin E1 and CDK2 proteins. Additionally, DOR induced apoptosis via the ROS-triggered mitochondrial pathway. This was attested by an elevation in the BAX/BCL-2 ratio, the activation of caspase 3/7 and the cleavage of PARP1. These mechanistic insights underscore DOR's potential as a therapeutic agent against cholangiocarcinoma.
format Artículo científico
id pubmed_39769205
institution PubMed
language en
publishDate 2024
publisher International journal of molecular sciences
record_format pubmed
spellingShingle Apoptosis-Inducing and Proliferation-Inhibiting Effects of Doramectin on Mz-ChA-1 Human Cholangiocarcinoma Cells.
Zhang, Yunfang
Wu, Wei
Shi, Yan
Huang, Yuehong
Dai, Ting
Ke, Lina
Chen, Lizhu
Chen, Mingliang
Wang, Qin
Humans
Cholangiocarcinoma
Cell Proliferation
Apoptosis
Ivermectin
Cell Line, Tumor
Bile Duct Neoplasms
Cell Movement
Reactive Oxygen Species
Antineoplastic Agents
Gene Expression Regulation, Neoplastic
Apoptosis-Inducing and Proliferation-Inhibiting Effects of Doramectin on Mz-ChA-1 Human Cholangiocarcinoma Cells. Zhang, Yunfang Wu, Wei Shi, Yan Huang, Yuehong Dai, Ting Ke, Lina Chen, Lizhu Chen, Mingliang Wang, Qin Humans Cholangiocarcinoma Cell Proliferation Apoptosis Ivermectin Cell Line, Tumor Bile Duct Neoplasms Cell Movement Reactive Oxygen Species Antineoplastic Agents Gene Expression Regulation, Neoplastic Cholangiocarcinoma is a malignant tumor that emerges in the intrahepatic or extrahepatic bile ducts. Doramectin (DOR), a third-generation derivative of avermectins (AVMs), is renowned for its low toxicity and high efficiency. However, no research has hitherto focused on the anti-cholangiocarcinoma effects of these drugs. In this study, we undertook a preliminary exploration of the mechanism through which DOR inhibits the viability of human cholangiocarcinoma cells (Mz-ChA-1) via transcriptome analysis and molecular validation at the cellular level. The results indicated that DOR could suppress the growth and proliferation of Mz-ChA-1 cells in a dose-dependent manner. Moreover, it significantly diminished their migration and invasion abilities. Cell cycle analysis disclosed arrest in the G1 phase, accompanied by an increase in p21 expression and a decrease in the levels of the cyclin E1 and CDK2 proteins. Additionally, DOR induced apoptosis via the ROS-triggered mitochondrial pathway. This was attested by an elevation in the BAX/BCL-2 ratio, the activation of caspase 3/7 and the cleavage of PARP1. These mechanistic insights underscore DOR's potential as a therapeutic agent against cholangiocarcinoma.
title Apoptosis-Inducing and Proliferation-Inhibiting Effects of Doramectin on Mz-ChA-1 Human Cholangiocarcinoma Cells.
topic Humans
Cholangiocarcinoma
Cell Proliferation
Apoptosis
Ivermectin
Cell Line, Tumor
Bile Duct Neoplasms
Cell Movement
Reactive Oxygen Species
Antineoplastic Agents
Gene Expression Regulation, Neoplastic
url https://pubmed.ncbi.nlm.nih.gov/39769205/