分类： 药物科学 >> 生物化学 提交时间： 2024-06-14
Huixu Feng
Guobin Liu
Luhan Li
Xuelian Ren
Yue Jiang
Wanting Hou
Ruilong Liu
Kun Liu
Hong Liu
He Huang
摘要： Hyperlipidemia (HLP) is a prevalent systemic metabolic disorder characterized by disrupted lipid metabolism. Statin drugs have long been the primary choice for managing lipid levels, but intolerance issues have prompted the search for alternative treatments. Matrine, a compound derived from the traditional Chinese medicine Kushen, exhibits anti-inflammatory and lipid-lowering properties. Nevertheless, the mechanism by which matrine modulates lipid metabolism remains poorly understood. Here, we investigated the molecular mechanisms underlying matrine’s regulation of lipid metabolism. Employing quantitative proteomics, we discovered that matrine increases the expression of LDL receptor (LDLR) in HepG2 and A549 cells, with subsequent experiments validating its role in enhancing LDL uptake. Notably, in hyperlipidemic hamsters, matrine effectively lowered lipid levels without affecting body weight, which highlights LDLR as a critical target for matrine’s impact on hyperlipidemia. Moreover, matrine’s potential inhibitory effects on tumor cell LDL uptake hint at broader applications in cancer research. Additionally, Thermal Proteome Profiling (TPP) analysis identified lipid metabolism-related proteins that may interact with matrine. Together, our study reveals matrine’s capacity to upregulate LDLR expression and highlights its potential in treating hyperlipidemia. These findings offer insights into matrine’s mechanism of action and open new avenues for drug research and lipid metabolism regulation.
分类： 药物科学 >> 生物化学 提交时间： 2024-06-14
Yue Jiang
Xuelian Ren
Jing Zhao
Guobin Liu
Fangfang Liu
Xinlong Guo
Ming Hao
Hong Liu
Kun Liu
He Huang
摘要： Gemcitabine (GEM) is a potent chemotherapeutic agent widely employed in the treatment of various cancers, notably pancreatic cancer. Despite its clinical success, challenges related to GEM resistance and toxicity persist. Therefore, there is a pressing need for a deeper understanding of its intracellular mechanisms and potential targets. In this study, we utilized quantitative proteomics and thermal proteome profiling (TPP) to elucidate the effects of GEM. Our proteomic analysis revealed that GEM primarily affected DNA synthesis, leading to the upregulation of cell cycle and DNA replication proteins. Additionally, enrichment analysis highlighted the activation of the p53 pathway, shedding light on GEM-induced apoptosis mechanisms. Notably, we observed the upregulation S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator, in response to GEM treatment. Combining SKP2 inhibition with GEM showed synergistic effects in both cellular and animal models, suggesting SKP2 as a potential target for enhancing GEM sensitivity and overcoming chemoresistance. Furthermore, through TPP, we explored potential binding targets of GEM, which implies GEM’s broad anticancer effects. Together, these findings provide valuable insights into GEM’s molecular mechanisms and offer potential targets for improving treatment efficacy. This research holds the promise of advancing personalized treatment strategies and opening avenues for novel combination therapies to enhance outcomes in pancreatic cancer.
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