基于蛋白质组学的洛伐他汀抑制食管鳞癌细胞增殖的机制。
The mechanism of lovastatin in suppressing the proliferation of esophageal squamous cell carcinoma based on proteomics.
机构信息
Department of Pathology Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
出版信息
J Gene Med. 2024 Aug;26(8):e3722. doi: 10.1002/jgm.3722.
BACKGROUND
Lovastatin, a type of statin usually considered as a lipid-lowering drug that lowers blood cholesterol and low-density lipoprotein cholesterol levels, has been rediscovered to have anticancer activity. Fewer studies exist regarding the effect of lovastatin on esophageal squamous cell carcinoma (ESCC).
METHODS
Here, we report that lovastatin shows anticancer effect on ESCC By affecting the mitochondrial autophagy pathway. Moreover, based on proteomics and computer molecular simulations found that RAB38 and RAB27A may be a target of lovastatin.
RESULTS
We observed that autophagy of mitochondria is inhibited by lovastatin, affecting esophageal squamous cell proliferation. There is a possible link between the expression of RAB38, RAB27A and immune cell invasion in esophageal cancer.
CONCLUSIONS
These results demonstrate the huge potential of lovastatin as an RAB38, RAB27A inhibitor in esophageal cancer chemotherapy and chemoprevention.
背景
洛伐他汀是一种他汀类药物，通常被认为是一种降脂药物，可降低血液胆固醇和低密度脂蛋白胆固醇水平，现已重新发现其具有抗癌活性。关于洛伐他汀对食管鳞状细胞癌（ESCC）的影响的研究较少。
方法
在这里，我们报道洛伐他汀通过影响线粒体自噬途径对 ESCC 表现出抗癌作用。此外，基于蛋白质组学和计算机分子模拟发现 RAB38 和 RAB27A 可能是洛伐他汀的靶点。
结果
我们观察到洛伐他汀抑制线粒体自噬，影响食管鳞状细胞增殖。RAB38、RAB27A 的表达与食管癌中免疫细胞浸润之间可能存在联系。
结论
这些结果表明，洛伐他汀作为 ESCC 化学治疗和化学预防中 RAB38、RAB27A 抑制剂具有巨大的潜力。
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