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.