Inhibition of Glutaminolysis Inhibits Cell Growth via Down-regulating Mtorc1 Signaling in Lung Squamous Cell Carcinoma

被引：13

作者：

Ye, Xulu ^{[1
]}

Zhou, Qiliang ^{[1
]}

Matsumoto, Yoshifumi ^{[1
]}

Moriyama, Masato ^{[1
]}

Kageyama, Shun ^{[2
]}

Komatsu, Masaaki ^{[2
]}

Satoh, Seijiro ^{[3
]}

Tsuchida, Masanori ^{[3
]}

Saijo, Yasuo ^{[1
]}

机构：

[1] Niigata Univ, Grad Sch Med & Dent Sci, Dept Med Oncol, 1-757 Asahimachi Dori Chuoh Ku, Niigata 9518510, Japan

[2] Niigata Univ, Grad Sch Med & Dent Sci, Dept Biochem, Niigata, Japan

[3] Niigata Univ, Grad Sch Med & Dent Sci, Dept Thorac Surg, Niigata, Japan

来源：

ANTICANCER RESEARCH | 2016年 / 36卷 / 11期

关键词：

Lung squamous cell carcinoma; molecular targeted therapy; glutaminolysis; glutaminase; BPTES; mTORC1; ACUTE MYELOID-LEUKEMIA; CANCER-CELLS; TUMOR-CELLS; GLUTAMINASE EXPRESSION; PROSTATE-CANCER; METABOLISM; PROLIFERATION; SUPPRESSION; AUTOPHAGY; BIOLOGY;

D O I：

10.21873/anticanres.11191

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：6021 / 6029

页数：9

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