ArticleOncoTargets and therapy2020
Irinotecan Induces Autophagy-Dependent Apoptosis and Positively Regulates ROS-Related JNK- and P38-MAPK Pathways in Gastric Cancer Cells.
Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting the PI3K/AKT/mTOR pathway in gastrointestinal cancers: a comprehensive review of mechanisms, preclinical evidence, and clinical challenges.Medical oncology (Northwood, London, England) · 2026Review
- IGFBP-3 enhances irinotecan efficacy in colorectal cancerResearch in pharmaceutical sciences · 2026Article
- Elp3 activates the JNK/MAPK pathway through histone acetylation to promote gastric cancer proliferation, migration, and invasion.Histology and histopathology · 2026Article
- Cancer therapy and cachexia.The Journal of clinical investigation · 2025Review
- EGb761 suppressed vascular dementia via modulating Wnt/β-catenin signaling pathway-induced apoptosis and autophagy in hippocampal neuronal cells.European journal of medical research · 2025Article
- Review
- Overcoming Irinotecan Resistance by Targeting Its Downstream Signaling Pathways in Colon Cancer.Cancers · 2024Article
- The impact of nanomaterials on autophagy across health and disease conditions.Cellular and molecular life sciences : CMLS · 2024Review
- Review
- Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer.International journal of molecular sciences · 2024Review
- Iron-Dependent Cell Death: A New Treatment Approach against Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Review
- The Cytoprotective Role of Autophagy in Response to BRAF-Targeted Therapies.International journal of molecular sciences · 2023Review
- P38 kinase in gastrointestinal cancers.Cancer gene therapy · 2023Review
- Single-cell analysis of gastric signet ring cell carcinoma reveals cytological and immune microenvironment features.Nature communications · 2023Article
- Resistance to TOP-1 Inhibitors: Good Old Drugs Still Can Surprise Us.International journal of molecular sciences · 2023Review
- Emetine, a small molecule natural product, displays potent anti-gastric cancer activity via regulation of multiple signaling pathways.Cancer chemotherapy and pharmacology · 2023Article
- P38 MAPK and Radiotherapy: Foes or Friends?Cancers · 2023Review
- Topoisomerase I poisons-induced autophagy: Cytoprotective, Cytotoxic or Non-protective.Autophagy reports · 2023Article
- IMMUNEPOTENT CRP increases intracellular calcium through ER-calcium channels, leading to ROS production and cell death in breast cancer and leukemic cell lines.EXCLI journal · 2023Article
- Mechanism of Elian granules in the treatment of precancerous lesions of gastric cancer in rats through the MAPK signalling pathway based on network pharmacology.Pharmaceutical biology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIrinotecan (IRI) is considered an option for second-line treatment of advanced gastric cancer; however, acquired drug resistance currently limits its clinical application. Recently, many researchers have shown that autophagy plays a crucial role in the resistance of tumor cells to chemotherapy and radiotherapy. In this study, we investigated the relationship between autophagy and antitumor activity of IRI in gastric cancer cells.
methodsWe used MTT assay, flow cytometry and immunofluorescence staining to detect viability, apoptosis and autophagy in gastric cancer. Western blotting assay was used to determine the expression of LC3, Beclin-1, P62, cleaved PARP and Caspase 3. In vivo animal study was performed finally.
resultsWe found that IRI treatment dose- and time-dependently inhibited growth and induced apoptosis in gastric cancer cells. Moreover, IRI treatment caused autophagy in these cells, whereas autophagy inhibitors-3-methyladenine (3-MA), chloroquine (CQ), and Beclin-1 small interfering RNA (siRNA)-suppressed cytotoxicity of IRI. A mechanistic analysis showed that IRI-induced autophagy and apoptosis were related to increased reactive oxygen species (ROS) accumulation and activation of the JNK- and p38-MAPK pathways. Further in vivo experiments revealed that IRI suppressed tumor growth, induced autophagy, and stimulated the JNK- and p38-MAPK pathways, whereas 3-MA attenuated these effects.
conclusionTaken together, these results indicate that IRI stimulates the ROS-related JNK- and p38-MAPK pathways to promote autophagy-dependent apoptosis. Thus, a combination of IRI with a pharmacological autophagy enhancer may be a promising therapeutic strategy against gastric cancer.
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