ArticleDrug design, development and therapy2017
Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells.
Article in Drug design, development and therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 115 citations in OpenAlex.
- Anchusa azurea enhances cisplatin efficacy in oral and bone cancers through IL-17 and TNF-α pathway modulation: a metabolomic and network pharmacology approach.Scientific reports · 2026Article
- Simultaneous activation and late-stage inhibition of autophagy induces autophagy-dependent cell death in leukemia.BMC cancer · 2026Article
- TLR7 induces autophagy in non-small cell lung cancer tumor cells and influences anti-tumors responses in patients.Translational lung cancer research · 2026Article
- Time-Dependent Effects of Cisplatin on Autophagy Gene Expression in Bladder Cancer Cells.Biomedicines · 2026Article
- Oxypalmatine promotes apoptosis and protective autophagy in lung cancer cells via the PI3K/AKT pathway.Cancer cell international · 2025Article
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- Advances in Targeted Autophagy Modulation Strategies to Treat Cancer and Associated Treatment-Induced Cardiotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Exploring Arylidene-Indolinone Ligands of Autophagy Proteins LC3B and GABARAP.ACS medicinal chemistry letters · 2025Article
- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Interfering Nuclear Protein Laminb1 Induces DNA Damage and Reduces Vemurafenib Resistance in Melanoma Cells In Vitro.Cancers · 2024Article
- Necroptosis and autophagy in cisplatinum-triggered nephrotoxicity: Novel insights regarding their prognostic and diagnostic potential.Toxicology reports · 2024Article
- Exploring Arylidene-Indolinone Ligands of Autophagy Proteins LC3B and GABARAP.bioRxiv : the preprint server for biology · 2024Article
- Halogenated Boroxine KMolecules (Basel, Switzerland) · 2024Article
- Advances in the molecular regulation mechanism of tumor dormancy and its therapeutic strategy.Discover oncology · 2024Review
- Oncopig bladder cancer cells recapitulate human bladder cancer treatment responsesFrontiers in oncology · 2024Article
- SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy.Cancers · 2023Article
- In silico study reveals unconventional interactions between MDC1 of DDR and Beclin-1 of autophagy.Molecular diversity · 2023Article
- The Molecular Mechanism and Therapeutic Application of Autophagy for Urological Disease.International journal of molecular sciences · 2023Review
- Pectolinarigenin inhibits bladder urothelial carcinoma cell proliferation by regulating DNA damage/autophagy pathways.Cell death discovery · 2023Article
- Targeting Pro-Survival Autophagy Enhanced GSK-3β Inhibition-Induced Apoptosis and Retarded Proliferation in Bladder Cancer Cells.Current oncology (Toronto, Ont.) · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC). Autophagy induction has been implied to contribute to cisplatin resistance in ovarian cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines. MATERIALS AND
methodsHuman BC cells (5637 and T24) were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3)-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL) formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1), chloroquine (CQ), and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12) were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation.
resultsCisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose-and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of cisplatin toward BC cells. These results indicated that cisplatin induced protective autophagy which may contribute to the development of cisplatin resistance and resulted in treatment failure. Mechanistically, upregulation of beclin-1 (BECN1) was detected in cisplatin-treated cells, and knockdown of BECN1 using shRNA attenuated cisplatin-induced autophagy and subsequently enhanced cisplatin-induced apoptosis.
conclusionCollectively, the study results indicated that cisplatin-induced autophagy is mediated by BECN1 in BC cells. Therefore, combinative treatment using cisplatin and autophagy inhibitors could potentially overcome cisplatin resistance related to autophagy induction.
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