Dataset Information

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway.

ABSTRACT:

Background

Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents.

Methods

The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels.

Results

Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2.

Conclusions

These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC.

SUBMITTER: Xu N

PROVIDER: S-EPMC8650430 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway.

Xu Nana N Lu Mengmeng M Wang Jiaxin J Li Yujia Y Yang Xiaotian X Wei Xiajie X Si Jiaoyang J Han Jingru J Yao Xiaojuan X Zhang Juanmei J Liu Junqi J Li Yanming Y Yang Hushan H Bao Dengke D

BMC cancer 20211207 1

<h4>Background</h4>Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents.<h4>Methods</h4>The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysf ...[more]

PMID: 34876051

Similar Datasets

Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is a common pathological esophageal cancer with poor prognosis. Vitamin D deficiency reportedly occurs in ESCC patients, and this is related to single nucleotide polymorphism of vitamin D receptor (VDR).ObjectiveWe investigated the effect of VDR on ESCC proliferation, invasion, and metastasis and its potential mechanism.MethodsESCC and normal tissues were collected from 20 ESCC patients. The ESCC tissue microarray contained 116 pairs of ESCC and normal tissues and 73 single ESCC tissues. VDR expression and its clinicopathological role were determined by real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry staining. sh-VDR and VDR overexpression were used to validate the effect of VDR on ESCC cell phenotype, and tandem mass tag-based quantitative proteomics and bioinformatics methods identified differential VDR-related proteins. The downstream pathway and regulatory effect were analyzed using ingenuity pathway analysis (IPA). Differentially expressed proteins were verified through parallel reaction monitoring and Western blot. In vivo imaging visualized subcutaneous tumor growth following tail vein injection of VDR-deficient ESCC cells.ResultsHigh VDR expression was observed in ESCC tissues and cells. Gender, T stage, and TNM stage were related to VDR expression, which was the independent prognostic factor related to ESCC. VDR downregulation repressed ESCC cell proliferation, invasion, and migration in vitro and subcutaneous tumor growth and lung metastases in vivo. The cell phenotype changes were reversed upon VDR upregulation, and differential proteins were mainly enriched in the p53 signaling pathway. TP53 cooperated with ABCG2, APOE, FTH1, GCLM, GPX1, HMOX1, JUN, PRDX5, and SOD2 and may activate apoptosis and inhibit oxidative stress, cell metastasis, and proliferation. TP53 was upregulated after VDR knockdown, and TP53 downregulation reversed VDR knockdown-induced cell phenotype changes.ConclusionsVDR may inhibit p53 signaling pathway activation and induce ESCC proliferation, invasion, and metastasis by activating oxidative stress.

Dataset Information

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway.

Background

Methods

Results

Conclusions

Publications

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets