ArticleInternational journal of molecular sciences2022
Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Glutamine Metabolism: Role in Cancer Cell Proliferation and Survival.Cancer treatment and research · 2026Review
- Preclinical Toxicity and Pharmacokinetic Evaluation of Paclitaxel Nanodispersion.AAPS PharmSciTech · 2025Article
- Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.Journal of ovarian research · 2025Review
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Genetic variations in amino acid metabolism-related genes are associated with risk of papillary thyroid carcinoma: a case-control study.BMC endocrine disorders · 2025Article
- Glutamine's double-edged sword: fueling tumor growth and offering therapeutic hope.Frontiers in immunology · 2025Review
- Proapoptotic role of CDK1 in overcoming paclitaxel resistance in ovarian cancer cells in response to combined treatment with paclitaxel and duloxetine.Cancer cell international · 2024Article
- IRE1α inhibitor enhances paclitaxel sensitivity of triple-negative breast cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Combination of Selenite and Butyrate Enhances Efficacy Against Colon Cancer by Targeting ASCT2-Mediated Amino Acid Metabolism.Biological trace element research · 2024Article
- Preclinical efficacy of CBR-5884 against epithelial ovarian cancer cells by targeting the serine synthesis pathway.Discover oncology · 2024Article
- Optimizing Paclitaxel Oral Absorption and Bioavailability: TPGS Co-Coating via Supercritical Anti-Solvent Fluidized Bed Technology.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The m-TORC1 inhibitor Sirolimus increases the effectiveness of Photodynamic therapy in the treatment of cutaneous Squamous Cell Carcinoma, impairing NRF2 antioxidant signaling.International journal of biological sciences · 2024Article
- Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.Frontiers in pharmacology · 2024Review
- Metabolic control of cancer metastasis: role of amino acids at secondary organ sites.Oncogene · 2023Review
- Tumor microenvironmental nutrients, cellular responses, and cancer.Cell chemical biology · 2023Review
- Synthesis of Polyethylene Glycol-Poly(glycerol carbonate) Block Copolymeric Micelles as Surfactant-Free Drug Delivery Systems.ACS macro letters · 2023Article
- Metabolic reprogramming of the ovarian cancer microenvironment in the development of antiangiogenic resistance.Acta biochimica et biophysica Sinica · 2023Review
- Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Childhood Acute Lymphoblastic Leukaemia Cells.International journal of molecular sciences · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Ovarian cancer is a carcinoma that affects women and that has a high mortality rate. Overcoming paclitaxel resistance is important for clinical application. However, the effect of amino acid metabolism regulation on paclitaxel-resistant ovarian cancer is still unknown. In this study, the effect of an amino acid-deprived condition on paclitaxel resistance in paclitaxel-resistant SKOV3-TR cells was analyzed. We analyzed the cell viability of SKOV3-TR in culture conditions in which each of the 20 amino acids were deprived. As a result, the cell viability of the SKOV3-TR was significantly reduced in cultures deprived of arginine, glutamine, and lysine. Furthermore, we showed that the glutamine-deprived condition inhibited mTORC1/S6K signaling. The decreased cell viability and mTORC1/S6K signaling under glutamine-deprived conditions could be restored by glutamine and α-KG supplementation. Treatment with PF-4708671, a selective S6K inhibitor, and the selective glutamine transporter ASCT2 inhibitor V-9302 downregulated mTOR/S6K signaling and resensitized SKOV3-TR to paclitaxel. Immunoblotting showed the upregulation of Bcl-2 phosphorylation and a decrease in Mcl-1 expression in SKOV3-TR via the cotreatment of paclitaxel with PF-4708671 and V-9302. Collectively, this study demonstrates that the inhibition of glutamine uptake can resensitize SKOV3-TR to paclitaxel and represents a promising therapeutic target for overcoming paclitaxel resistance in ovarian cancer.
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