抑制谷氨酰胺分解通过下调肺鳞状细胞癌中的Mtorc1信号传导来抑制细胞生长。
Inhibition of Glutaminolysis Inhibits Cell Growth via Down-regulating Mtorc1 Signaling in Lung Squamous Cell Carcinoma.
作者信息
Ye Xulu, Zhou Qiliang, Matsumoto Yoshifumi, Moriyama Masato, Kageyama Shun, Komatsu Masaaki, Satoh Seijiro, Tsuchida Masanori, Saijo Yasuo
机构信息
Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
出版信息
Anticancer Res. 2016 Nov;36(11):6021-6029. doi: 10.21873/anticanres.11191.
BACKGROUND/AIM: Inhibition of glutaminolysis has been reported as a promising therapeutic strategy to target several solid carcinomas. We aimed to investigate the effects of glutaminolysis on cell proliferation in lung squamous cell carcinoma cell lines and to explore the potential of targeting glutaminolysis as an anticancer strategy.
MATERIALS AND METHODS
Glutamine (Gln) dependence was assessed in six lung squamous cell carcinoma cell lines. Cell proliferation, mammalian target of rapamycin complex 1 (mTORC1) activity and the induction of autophagy were assessed after inhibition of glutaminolysis via Gln depletion or glutaminase (GLS) inhibition.
RESULTS
Five of six lung squamous cell carcinoma cell lines exhibited glutamine-dependence. The extent of dependence was correlated with the mRNA levels of GLS1/GLS2. Inhibition of glutaminolysis inhibited cell proliferation by down-regulating of mTORC1 signaling and inducing autophagy in Gln-dependent lung squamous cell carcinoma cell lines.
CONCLUSION
Targeting glutaminolysis may represent a potential therapeutic strategy for the treatment of Gln-dependent lung squamous cell carcinomas.
背景/目的：已有报道称，抑制谷氨酰胺分解是一种针对多种实体癌的有前景的治疗策略。我们旨在研究谷氨酰胺分解对肺鳞状细胞癌细胞系中细胞增殖的影响，并探索将靶向谷氨酰胺分解作为一种抗癌策略的潜力。
材料与方法
评估了六种肺鳞状细胞癌细胞系对谷氨酰胺（Gln）的依赖性。通过Gln耗竭或谷氨酰胺酶（GLS）抑制来抑制谷氨酰胺分解后，评估细胞增殖、雷帕霉素复合物1的哺乳动物靶点（mTORC1）活性以及自噬的诱导情况。
结果
六种肺鳞状细胞癌细胞系中有五种表现出谷氨酰胺依赖性。依赖程度与GLS1/GLS2的mRNA水平相关。在依赖Gln的肺鳞状细胞癌细胞系中，抑制谷氨酰胺分解通过下调mTORC1信号传导和诱导自噬来抑制细胞增殖。
结论
靶向谷氨酰胺分解可能是治疗依赖Gln的肺鳞状细胞癌的一种潜在治疗策略。
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