Triptolit: Küçük Hücreli Akciğer Kanserinin Önemli Fraksiyonunun lncRNA'lar aracılı Hücresel Metabolizmasının Düzenleyicisi

Amaç: Küçük hücreli akciğer kanseri (KHAK), tüm akciğer kanseri vakalarının %15'ini oluşturmaktadır. Myc ailesi, küçük hücreli akciğer kanserlerinin %20'sinde sıklıkla amplifiye/ aşırı eksprese edilir ve karsinogenezi indüklemektedir. Bir Çin şifalı bitkisi olan Triptolit, Tripterygium wilfordii Hook f 'den izole edilen bir antikanser moleküldür. Bu çalışma, Triptolit'in Myc aşırı eksprese/amplifiye KHAK hücreleri üzerindeki olası etkisini araştırmayı amaçlamıştır. Materyal ve metod: Myc ve Myc'ye bağlı metabolik genlerin ekspresyonunu belirlemek için H209, H209myc, N417 ve Lu135 hücreleri Triptolit ile muamele edildi ve Myc ve ilişkili lncRNA'ların ekspresyon seviyeleri qRT-PCR ile analiz edildi. Myc, p21, siklin D1 protein ifadelerini değerlendirmek için Western blot analizi yapıldı. Ayrıca, triptolit ile muamele edilmiş hücrelerde glikoz alınım aktivitesi ölçüldü. Bulgular: Triptolit'in MYC ekspresyonunu inhibe ederek KHAK hücrelerinin proliferasyonunu baskıladığını gözlemledik. Triptolitin hücresel proliferasyonu, glikoz metabolizmasını ve glikoz alımını inhibe ettiği ve Glut1, Glut4, HK2, LDHA ve Eno1 ifadelerinde azalmaya neden olduğu saptandı. Triptolit’in hücresel proliferasyon ve metabolizma ile ilişkili lncRNA'ların (ANRIL, PVT1, PTENP1, H19 ve lincRNA-p21) ifadelerini düzenlediği gözlemlendi. Sonuç: Sonuçlar, triptolit tedavisinin lncRNA ekspresyonlarını düzenleyerek hücresel proliferasyonu ve glikoz metabolizmasını baskıladığını güçlü bir şekilde göstermiştir. Triptolit tedavisinin KHAK için umut verici bir terapötik strateji olacağını düşünmekteyiz.

Anahtar Kelimeler:

Triptolit, Küçük hücreli akciğer kanseri, MYC, lncRNA, Metabolizma

Triptolide: Regulator of Cellular Metabolism of Significant Fraction of Small Cell Lung Cancer via lncRNAs

Objective: Small cell lung cancer accounts for 15% of all lung cancer cases. Myc family is frequently amplified and/or overexpressed in 20% of small cell lung cancers and can promote carcinogenesis. Triptolide, a Chinese medicinal herb, is an anticancer reagent isolated from Tripterygium wilfordii Hook f. This study aimed to investigate Triptolide's possible effect on Myc overexpressed/ amplified SCLC cells. Materials and methods: To determine the expression of Myc and Myc-dependent metabolic genes, H209, H209myc, N417, and Lu135 cells were treated with Triptolide, and expression levels of Myc and associated lncRNAs were measured by qRT-PCR. Western blot analysis was performed to evaluate Myc, p21, cyclin D1 expressions. Besides, glucose uptake activity was assessed in the triptolide-treated cells. Results: We have observed that Triptolide inhibited the proliferation of SCLC cells by inhibiting MYC expression. Triptolide has been found to repress cellular proliferation, glucose metabolism, and glucose uptake, resulting in decreased Glut1, Glut4, HK2, LDHA, and Eno1. Triptolide changed the expressions of cellular proliferation and metabolism-related lncRNAs (ANRIL, PVT1, PTENP1, H19, and lincRNA-p21). Conclusion: The results have strongly indicated that triptolide treatment reduces cellular proliferation and glucose metabolism by regulating lncRNA expressions. Triptolide treatment would be a promising therapeutic strategy for SCLC.

Keywords:

Triptolide, Small cell lung cancer, MYC, lncRNA, Metabolism,

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