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抑制谷氨酰胺摄取通过 mTORC1/S6K 信号通路使紫杉醇耐药的 SKOV3-TR 卵巢癌细胞重新敏感。

Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway.

机构信息

Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Korea.

Department of Cosmetics Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea.

出版信息

Int J Mol Sci. 2022 Aug 6;23(15):8761. doi: 10.3390/ijms23158761.

DOI:10.3390/ijms23158761
PMID:35955892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9369036/
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.

摘要

卵巢癌是一种影响女性的癌，死亡率很高。克服紫杉醇耐药性对于临床应用很重要。然而，氨基酸代谢调节对紫杉醇耐药性卵巢癌的影响尚不清楚。在本研究中，分析了氨基酸剥夺条件对紫杉醇耐药 SKOV3-TR 细胞紫杉醇耐药性的影响。我们分析了 SKOV3-TR 在每种 20 种氨基酸都被剥夺的培养条件下的细胞活力。结果，在缺乏精氨酸、谷氨酰胺和赖氨酸的培养物中，SKOV3-TR 的细胞活力显著降低。此外，我们表明，谷氨酰胺剥夺条件抑制了 mTORC1/S6K 信号。谷氨酰胺剥夺条件下降低的细胞活力和 mTORC1/S6K 信号可以通过补充谷氨酰胺和 α-KG 来恢复。用选择性 S6K 抑制剂 PF-4708671 和选择性谷氨酰胺转运体 ASCT2 抑制剂 V-9302 处理可下调 mTOR/S6K 信号，并使 SKOV3-TR 对紫杉醇重新敏感。免疫印迹显示，通过紫杉醇与 PF-4708671 和 V-9302 的联合治疗，SKOV3-TR 中 Bcl-2 磷酸化上调，Mcl-1 表达下调。总之，本研究表明，抑制谷氨酰胺摄取可以使 SKOV3-TR 对紫杉醇重新敏感，是克服卵巢癌紫杉醇耐药性的有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ff/9369036/7d28c9e4645c/ijms-23-08761-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ff/9369036/be5f184f1869/ijms-23-08761-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ff/9369036/f8007be8b434/ijms-23-08761-g002.jpg
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2
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CA Cancer J Clin. 2022 Jan;72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12.
3
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细胞周期蛋白依赖性激酶1（CDK1）在卵巢癌细胞中对紫杉醇和度洛西汀联合治疗产生反应时克服紫杉醇耐药性方面的促凋亡作用。
Cancer Cell Int. 2024 Dec 19;24(1):409. doi: 10.1186/s12935-024-03607-8.
4
Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers.小细胞外囊泡在癌症代谢重编程和耐药性中的新作用
Cancer Drug Resist. 2024 Sep 27;7:38. doi: 10.20517/cdr.2024.81. eCollection 2024.
5
The m-TORC1 inhibitor Sirolimus increases the effectiveness of Photodynamic therapy in the treatment of cutaneous Squamous Cell Carcinoma, impairing NRF2 antioxidant signaling.mTORC1 抑制剂西罗莫司提高光动力疗法治疗皮肤鳞状细胞癌的疗效，抑制 NRF2 抗氧化信号。
Int J Biol Sci. 2024 Aug 6;20(11):4238-4257. doi: 10.7150/ijbs.94883. eCollection 2024.
6
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Discov Oncol. 2024 May 11;15(1):154. doi: 10.1007/s12672-024-01013-0.
7
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9
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10
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