ArticleCell proliferation2019
Inhibition of PI3K/mTOR increased the sensitivity of hepatocellular carcinoma cells to cisplatin via interference with mitochondrial-lysosomal crosstalk.
Article in Cell proliferation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Research Progress on Quinone Compounds for the Treatment of Hepatocellular Carcinoma.Biomolecules · 2025Review
- Overexpression of c-Myc triggers p62 aggregation-mediated mitochondrial mitophagy in cabozantinib resistance of hepatocellular carcinoma.Molecular medicine (Cambridge, Mass.) · 2025Article
- Carrier-Free Cisplatin-Dactolisib Nanoparticles for Enhanced Synergistic Antitumor Efficacy.ACS biomaterials science & engineering · 2025Article
- Review
- Mitochondria-associated non-coding RNAs and their impact on drug resistance.Frontiers in pharmacology · 2025Review
- Autophagy-based therapy for hepatocellular carcinoma: from standard treatments to combination therapy, oncolytic virotherapy, and targeted nanomedicines.Clinical and experimental medicine · 2024Review
- Article
- Ailanthone blocks mitophagy to promote mtDNA leakage through BAX-BAK1 pores and suppress hepatocellular carcinoma cell proliferation.Frontiers in pharmacology · 2024Article
- The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics.International journal of molecular sciences · 2023Review
- Cisplatin ototoxicity mechanism and antagonistic intervention strategy: a scope review.Frontiers in cellular neuroscience · 2023Review
- The transcription factor c-Jun inhibits RBM39 to reprogram pre-mRNA splicing during genotoxic stress.Nucleic acids research · 2022Article
- Mitophagy: A novel perspective for insighting into cancer and cancer treatment.Cell proliferation · 2022Review
- Article
- Autophagy plays a double-edged sword role in liver diseases.Journal of physiology and biochemistry · 2022Review
- Overexpression of E74-like transformation-specific transcription factor 3 promotes cellular proliferation and predicts poor prognosis in ovarian cancer.Oncology letters · 2021Article
- Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways.International journal of oncology · 2021Article
- Evaluation of mitochondria in mouse oocytes following cisplatin exposure.Journal of ovarian research · 2021Article
- Autophagy, an accomplice or antagonist of drug resistance in HCC?Cell death & disease · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesThe genotoxicity of cisplatin towards nuclear DNA is not sufficient to explain the cisplatin resistance of hepatocellular carcinoma (HCC) cells; cisplatin interacts with many organelles, which can influence the sensitivity. Here, we explored the role of mitochondrial-lysosomal crosstalk in the cisplatin resistance of HCC cells. MATERIALS AND
methodsHuh7 and HepG2 cells were subjected to different treatments. Flow cytometry was conducted to detect mitochondrial reactive oxygen species, mitochondrial mass, lysosomal function, mitochondrial membrane potential and apoptosis. Western blotting was performed to evaluate protein levels. The oxygen consumption rate was measured to evaluate mitochondrial function.
resultsCisplatin activated mitophagy and lysosomal biogenesis, resulting in crosstalk between mitochondria and lysosomes and cisplatin resistance in HCC cells. Furthermore, a combination of cisplatin with the phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor PKI-402 induced lysosomal membrane permeabilization. This effect changed the role of the lysosome from a protective one to that of a cell death promoter, completely destroying the mitochondrial-lysosomal crosstalk and significantly enhancing the sensitivity of HCC cells to cisplatin.
conclusionsThis is the first evidence of the importance of mitochondrial-lysosomal crosstalk in the cisplatin resistance of HCC cells and of the destruction of this crosstalk by a PI3K/mTOR inhibitor to increase the sensitivity of HCC cells to cisplatin. This mechanism could be developed as a novel target for treatment of HCC in the future.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.