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Sorafenib, as a multi-kinase inhibitor, was the first FDA-approved anti- hepatocellular carcinoma (HCC) drug. Rhizoma Paridis saponins (RPS) as natural products have shown antitumor activity through regulation of glycolytic and lipid metabolism which was regarded as the side effect limited the utility of sorafenib. In this research, we tried to use metabolomics to verify the probability of combinatorial treatment of RPS and Sorafenib. As a result, Sorafenib + RPS increased the antitumor effect of sorafenib and RPS in H22 mice. They mitigated the change of liver weight and the increasing levels of AST and ALT in serum, and AFP and MDA in liver tissues, which indicated their liver protective activity. They also up-regulated the activity of NOX and SDH, concentration of ATP, and down-regulated the mRNA and protein levels of HIF-1a and concentration of lactate, which suggested they protected against mitochondria damage and inhibited anaerobic glycolysis. Meanwhile, the combination group remarkably down-regulated the concentration of octadecanoic acid and hexadecanoic acid in serum, and tetradecanoic acid in liver tissues compared with model group (p < 0.05). Relative regulation mechanism included their decreasing mRNA levels of FASN, CPT1, GLUT1, Myc, Akt, mTOR and LDHA, and increasing the protein expression of p53 in tumor and liver tissues (p < 0.05). Furthermore, similar influence can be observed in protein levels of CPT1A, p-PI3K, p-mTOR and p53 in liver tissues and FASN in serum. All of that provided possibility to overcome the intolerance of sorafenib by drug compatibility through protection against mitochondria damage, inhibition of anaerobic glycolysis and suppression of lipid synthesis based on PI3K/Akt/mTOR pathway.
This article was published in the following journal.
Name: The Journal of steroid biochemistry and molecular biology
Kinase inhibitor sorafenib is the most widely used drug for advanced HCC clinical treatment nowadays. However, sorafenib administration is only effective for a small portion of HCC patients, and the m...
Hepatocellular carcinoma (HCC) is a highly invasive cancer associated with high mortality rates. Although sorafenib is currently recommended as standard treatment for advanced HCC, its treatment effic...
The clinical application of sorafenib is limited because of its hydrophobicity, low bioavailability and unsatisfying treatment effect. Therefore, sorafenib-loaded PEG-poly (ε-caprolactone) micelles (...
The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be appro...
Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Sorafenib is the only FDA approved first-line targeted drug for advanced HCC, but its effect on patients'...
This is a randomized double-blind placebo controlled trial aim to compare the efficiency of genuine regional and non-genuine regional Rhizoma Atractylodis in treating functional dyspepsia....
The purpose of this study is to determine whether panax notoginseng saponins are effective in the treatment of Hypertensive Intracerebral Hemorrhage Patients.
The purpose of this study is to find out what effects, good and/or bad, the combination of sorafenib and temsirolimus will have on thyroid cancer. Treatment guidelines from the National Co...
RFA is a routaine treatment of recurrent HCC. Recently Sorafenib was reported to be a promising drug to treat late stage HCC. But few studies were related with its effectiveness on recurre...
The principal objective of this study is to explore the role of 18F-FDG PET in identifying sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease outco...
Allergic reaction to milk (usually cow's milk) or milk products. MILK HYPERSENSITIVITY should be differentiated from LACTOSE INTOLERANCE, an intolerance to milk as a result of congenital deficiency of lactase.
The condition resulting from the absence or deficiency of LACTASE in the MUCOSA cells of the GASTROINTESTINAL TRACT, and the inability to break down LACTOSE in milk for ABSORPTION. Bacterial fermentation of the unabsorbed lactose leads to symptoms that range from a mild indigestion (DYSPEPSIA) to severe DIARRHEA. Lactose intolerance may be an inborn error or acquired.
A chemistry-based technology in which sets of reactions, for solution or solid-phase synthesis, are used to create molecular libraries for analysis of compounds on a large scale.
A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
Organic chemistry methodology that mimics the modular nature of various biosynthetic processes. It uses highly reliable and selective reactions designed to "click" i.e., rapidly join small modular units together in high yield, without offensive byproducts. In combination with COMBINATORIAL CHEMISTRY TECHNIQUES, it is used for the synthesis of new compounds and combinatorial libraries.
In order to become availible to pateints, drugs need to undergo a number of phases of clinical trials to test their efficacy and safty and to then be authorised by the drug approval organistion in each respective country. This is the FDA in the USA and N...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...