ArticleJournal of experimental & clinical cancer research : CR2013
Suppression of autophagy enhances preferential toxicity of paclitaxel to folliculin-deficient renal cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Relationship between different modes of death and premature ovarian insufficiency: a literature review.Apoptosis : an international journal on programmed cell death · 2026Review
- Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.Cancers · 2023Review
- Lipid metabolism-related gene expression in the immune microenvironment predicts prognostic outcomes in renal cell carcinoma.Frontiers in immunology · 2023Article
- Mechanisms of cancer cell death induction by paclitaxel: an updated review.Apoptosis : an international journal on programmed cell death · 2022Review
- Adaptor SH3BGRL drives autophagy-mediated chemoresistance through promoting PIK3C3 translation and ATG12 stability in breast cancers.Autophagy · 2022Article
- Cuproptosis-related lncRNA signatures predict prognosis and immune relevance of kidney renal papillary cell carcinoma.Frontiers in pharmacology · 2022Article
- Overexpression of TP53INP2 Promotes Apoptosis in Clear Cell Renal Cell Cancer via Caspase-8/TRAF6 Signaling Pathway.Journal of immunology research · 2022Article
- Research Progress and Prospects of Autophagy in the Mechanism of Multidrug Resistance in Tumors.Journal of oncology · 2022Review
- Is targeting autophagy mechanism in cancer a good approach? The possible double-edge sword effect.Cell & bioscience · 2021Review
- Targeting Cytoprotective Autophagy to Enhance Anticancer Therapies.Frontiers in oncology · 2021Review
- Implications on the Therapeutic Potential of StatinsOxidative medicine and cellular longevity · 2021Review
- The Unfolded Protein Response: Neutron-Induced Therapy Autophagy as a Promising Treatment Option for Osteosarcoma.International journal of molecular sciences · 2020Article
- Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy.Frontiers in pharmacology · 2020Review
- Pulmonary-Affinity Paclitaxel Polymer Micelles in Response to Biological Functions of Ambroxol Enhance Therapeutic Effect on Lung Cancer.International journal of nanomedicine · 2020Article
- Autophagy as a Vital Therapy Target for Renal Cell Carcinoma.Frontiers in pharmacology · 2020Review
- Involvement of Actin in Autophagy and Autophagy-Dependent Multidrug Resistance in Cancer.Cancers · 2019Review
- Autophagy Machinery as a Promising Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
- Role of Autophagy in Renal Cancer.Journal of Cancer · 2019Review
- Paclitaxel increases the sensitivity of lung cancer cells to lobaplatin via PI3K/Akt pathway.Oncology letters · 2018Article
- Silencing Aurora A leads to re-sensitization of breast cancer cells to Taxol through downregulation of SRC-mediated ERK and mTOR pathways.Oncology reports · 2017Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPaclitaxel, a widely used chemotherapeutic drug, can induce apoptosis in variety of cancer cells. A previous study has shown preferential toxicity of paclitaxel to FLCN-deficient kidney cancer cell line, UOK257. In this report, we investigate the cellular and molecular mechanism of paclitaxel-induced autophagy and apoptosis in renal cancer cells with and without FLCN expression.
methodsTwo pairs of cell lines were used: FLCN siRNA-silenced ACHN cell line (ACHN-5968) and scrambled ACHN cell line (ACHN-sc); FLCN-null UOK257 cell line and UOK257-2 cell line restored with ectopic expression of FLCN. Autophagy was examined by western blot, GFP-LC3, transmission electron microscopy, and MDC assay. Cell viability and apoptosis were detected using MTT assay, DAPI stain and TUNEL assay. After inhibition of autophagy with 3-Methyladenine (3-MA) or Beclin 1 siRNA, cell viability and apoptosis were measured by MTT assay and TUNEL assay.
resultsAfter paclitaxel treatment, a dose-dependent decrease in cell viability and increase in apoptosis were observed in FLCN-deficient UOK257 and ACHN-5968 cells compared to their FLCN-expressing counterparts, suggesting that renal cancer cells without FLCN were more sensitive to paclitaxel. Enhanced autophagy was found to be associated with paclitaxel treatment in FLCN-deficient RCC cells. The MAPK pathway was also identified as a key pathway for the activation of autophagy in these kidney cancer cells. Inhibition of phosphorylated ERK with ERK inhibitor U0126 showed a significant decrease in autophagy. Furthermore, after inhibition of autophagy with 3-Methyladenine (3-MA) or Beclin 1 siRNA, apoptosis induced by paclitaxel was significantly increased in FLCN-deficient UOK257 and ACHN-5968 cells.
conclusionsPreferential toxicity of paclitaxel to FLCN-deficient kidney cancer cells is associated with enhanced autophagy. Suppression of autophagy further enhances paclitaxel-induced apoptosis in FLCN-deficient renal cancer cells. Our results suggest that paclitaxel combined with an autophagy inhibitor might be a potentially more effective chemotherapeutic approach for FLCN-deficient renal cancer.
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