| Project/Area Number |
17K15020
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肺扁平上皮癌 / グルタミン / 分子標的治療 |
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| Outline of Final Research Achievements |
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. 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. 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.
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| Academic Significance and Societal Importance of the Research Achievements |
肺扁平上皮癌細胞株の多くはグルタミン代謝依存性で、Gls1 阻害剤による治療効果が十分期待できる。よって、分子標的治療薬が存在しない肺扁平上皮癌に対する新たな分子標的治療になる可能性が十分ある。一方、グルタミン代謝依存性に関わる遺伝子異常は、TP53, c-myc, Nrf2 がある。更には、神経膠芽腫や急性白血病にみられる IDH1遺伝子異常においてもグルタミン依存性が示されている。よってグルタミン代謝酵素であるグルタミナーゼをターゲットとした分子標的薬を開発する端緒となれば、これら遺伝子異常を持つ様々ながん腫に効果を発揮する可能性が高く、多くの患者の福音となる可能性がある。
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