Mevalonate (lithium salt) is a metabolic precursor of the mevalonate pathway[1]. As a substrate supplement for this pathway, Mevalonate (lithium salt) is mainly utilized to investigate its key role in cell growth, proliferation, cholesterol synthesis, and protein prenylation[2]. Mevalonate (lithium salt) is commonly used in research on cardiovascular diseases, neurological disorders, metabolic diseases, and cancer[3][4].
In vitro, treatment of FRTL-5 thyroid epithelial cells with Mevalonate (lithium salt) (700µM; 2h) completely reversed mevinolin-induced cytoskeletal disruption, restored polygonal morphology, reorganized actin stress fibers and cortical actin networks, and re-established microtubule architecture[5]. Mevalonate (lithium salt) (5-20mM; 8-72h) dose-dependently inhibited acid sphingomyelinase activity, increased cellular cholesterol levels, elevated sphingomyelin and phosphatidylcholine content, and suppressed proliferation in HepG2 and Caco-2 cells[6].
In vivo, Mevalonate (lithium salt) (100mg/kg/day; i.p.; 14 days) enhanced anti-PD-L1 antibody efficacy, upregulated tumor PD-L1 expression, increased CD8+ and CD3+ T cell infiltration, and elevated IFN-γ, IL-2, and TNF-α secretion in CT26 colon cancer-bearing BALB/c mice[7].
References:
[1] Dellas N, Thomas ST, Manning G, Noel JP. Discovery of a metabolic alternative to the classical mevalonate pathway. Elife. 2013;2:e00672.
[2] Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990;343(6257):425-430.
[3] Buhaescu I, Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clin Biochem. 2007;40(9-10):575-584.
[4] Juarez D, Fruman DA. Targeting the Mevalonate Pathway in Cancer. Trends Cancer. 2021;7(6):525-540.
[5] Bifulco M, Laezza C, Aloj SM, Garbi C. Mevalonate controls cytoskeleton organization and cell morphology in thyroid epithelial cells. J Cell Physiol. 1993;155(2):340-348.
[6] Chen Y, Xu SC, Duan RD. Mevalonate inhibits acid sphingomyelinase activity, increases sphingomyelin levels and inhibits cell proliferation of HepG2 and Caco-2 cells. Lipids Health Dis. 2015;14:130.
[7] Zhang W, Pan X, Xu Y, et al. Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA. Acta Pharm Sin B. 2023;13(6):2585-2600.
Mevalonate (lithium salt)是甲羟戊酸途径的代谢前体[1]。Mevalonate (lithium salt)作为甲羟戊酸途径的底物补充剂，主要用于研究该途径在细胞生长、增殖、胆固醇合成及蛋白质异戊二烯化中的关键作用[2]。Mevalonate (lithium salt)通常用于心血管疾病、神经疾病、代谢疾病及癌症研究[3][4]。
在体外实验中，Mevalonate (lithium salt)（700µM；2小时）完全逆转了mevinolin诱导的FRTL-5甲状腺上皮细胞骨架破坏，恢复了多边形形态，重组了肌动蛋白应力纤维和皮质肌动蛋白网络，并重建了微管结构[5]。Mevalonate (lithium salt)（5-20mM；8-72小时）呈剂量依赖性抑制HepG2和Caco-2细胞中的酸性鞘磷脂酶活性，上调细胞内胆固醇水平，增加鞘磷脂和磷脂酰胆碱含量，并抑制细胞增殖[6]。
在体内实验中，Mevalonate (lithium salt)（100mg/kg/天；腹腔注射；14天）增强了抗PD-L1抗体的疗效，上调了肿瘤PD-L1表达，增加了CD8⁺和CD3⁺ T细胞浸润，并提升了CT26结肠癌荷瘤BALB/c小鼠肿瘤组织中IFN-γ、IL-2和TNF-α的分泌水平[7]。