Abstract:
BACKGROUND:Rho-Associated kinases ROCK1 and ROCK2 have been extensively investigated in the pathogenesis of cardiovascular disease. However, their roles are not fully understood in carcinogenesis. In this study, we investigated whether ROCK1 or ROCK2 is required for the survival and growth of hepatocellular carcinoma (HCC) cells and underlying mechanism. METHODS:ROCKs expression was determined in human HCC tissue and cell lines using qRT-PCR, western blotting, and immunohistochemistry (IHC). Cell growth and proliferation were assayed using cell counting kit-8 (CCK-8) and EdU incorporation assay. Cell cycle and apoptosis analysis were performed using flow cytometry. HCC cell division or mitosis was observed using a confocal microscope and a time relapse fluorescence microscope. Inhibitory role of targeting ROCK1/2 on HCC was assayed in both xenograft and primary HCC mouse models. RESULTS:Both ROCK1 and ROCK2 are over-expressed in human HCC tissues and cell lines. Knockdown of ROCK1 or ROCK2 inhibited HCC cell growth. Pharmacological inactivation of ROCK1/2 with Fasudil further blocked the growth and survival of HCC both in vitro and in vivo. Mechanically, Fasudil induces cell cycle arrest in HCC cells, but not apoptosis. Instead, Fasudil treatment led to mitotic catastrophe in HCC cells, characterized with the multipolar and asymmetric mitosis, and disassociated stress fibers. Knockdown of cofilin restored the cell morphology and division, and reduced the mitotic catastrophe induced by Fasudil. CONCLUSIONS:Both ROCK1 and ROCK2 are required for HCC cell division and growth. Targeting ROCK1 or ROCK2 rather than both can serve as a potential approach for HCC treatment and may reduce the side effects.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Wu H,Chen Y,Li B,Li C,Guo J,You J,Hu X,Kuang D,Qi S,Liu P,Li L,Xu Cdoi
10.1016/j.bcp.2020.114353subject
Has Abstractpub_date
2020-12-02 00:00:00pages
114353eissn
0006-2952issn
1873-2968pii
S0006-2952(20)30589-Xjournal_volume
184pub_type
杂志文章abstract::Two novel halogenated pyrrolopyrimidine analogues of adenosine, isolated from marine sources, have been examined for pharmacological and biochemical activities. 4-Amino-5-bromo-pyrrolo[2,3-d]pyrimidine, from a sponge of the genus Echinodictyum, had bronchodilator activity at least as potent as theophylline but with a ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90225-9
更新日期:1984-02-01 00:00:00
abstract::With the completion of the genome of Mycobacterium tuberculosis comes the promise of a new generation of potent drugs to combat the emerging epidemic of multiply drug-resistant isolates. Translating this genomic information into realistic assays, valid targets, and preclinical drug candidates represents the next great...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00253-1
更新日期:2000-02-01 00:00:00
abstract::5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) is a commonly used pharmacological agent to study physiological effects which are similar to those of exercise. However, signal transduction pathways by which AICAR elicits downstream effects in liver are poorly understood. We report here that AICAR not on...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.08.028
更新日期:2008-01-15 00:00:00
abstract::Alcohol-fed hamsters were used to study the mechanism by which acetaminophen initiates hepatotoxicity. Animals maintained on an ethanol-containing diet (Group B) exhibited an increased mortality rate after administration of acetaminophen (400 mg/kg) as compared to control hamsters (Group A). However, in those animals ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90426-4
更新日期:1983-07-01 00:00:00
abstract::(-)-2'-deoxy-3'-thiacytidine (3TC) has been shown to be a potent, selective inhibitor of HIV replication in vitro, which requires phosphorylation to its 5'-triphosphate for antiviral activity. The intracellular concentration of 3TC 5'-triphosphate in phytohaemagglutinin (PHA)-stimulated peripheral blood lymphocytes (P...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)96620-a
更新日期:1995-09-28 00:00:00
abstract::The partition coefficients (Kp) of three prototype Ca2+ antagonists, nitrendipine, (-)-desmethoxyverapamil and flunarizine were determined in native synaptic plasma membranes (SPM) isolated from sheep brain cortex and in liposomes prepared with the total lipids extracted from the membranes. We found that at 25 degrees...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90066-x
更新日期:1989-07-01 00:00:00
abstract::Uptake of two ellipticine derivatives, 2-N-methyl-ellipticinium (NME) and 2-N-methyl-9-hydroxy-ellipticinium, by sensitive and resistant Chinese hamster lung cells was studied. The results show that uptake and retention of these molecules by both types of cells were identical, thus indicating that the resistance to el...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90622-6
更新日期:1983-03-15 00:00:00
abstract::The interactions of the anticonvulsant drug milacemide (2-n-pentylaminoacetamide) with rat liver mitochondrial monoamine oxidases-A and -B have been studied. The compound acts as a substrate for the B-form of the enzyme, with an apparent Km value of 49 +/- 4.7 microM and a Vmax value of 1.1 +/- 0.2 nmol/min/mg. It is ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90123-6
更新日期:1994-02-11 00:00:00
abstract::A series of protein modifying reagents were tested for their effects on the specific binding of [3H]MK801 to adult rat brain membranes. N-Bromosuccinimide, acetyl imidazole, 2,3-butanedione, 5,5'-dithiobis-(2-nitrobenzoic acid) and dithiothreitol all had no significant effect on binding. The carboxylic acid residue mo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90133-h
更新日期:1993-02-09 00:00:00
abstract::A form of cytochrome P-450, P-450-D3, cross reactive with antibodies to rat P-450d was purified from liver microsomes of polychlorinated biphenyl (PCB)-treated female Beagle dogs to an electrophoretic homogeneity. Judging from the result of sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the molec...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90154-8
更新日期:1989-01-01 00:00:00
abstract::The alkanes, ethane and pentane, are often used as indices of lipid peroxidation. Because it has been indicated that O2 tension can affect the yield of these compounds, a systematic study of this was carried out. Rat liver microsomes were peroxidized using an iron-ascorbate system. The incubations were carried out in ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90186-9
更新日期:1987-03-15 00:00:00
abstract::Uteroglobin, a steroid-dependent secretory protein first discovered in the rabbit uterus during early pregnancy, is a potent phospholipase A2 inhibitor. We found that uteroglobin also inhibited human and rabbit phagocyte chemotaxis in response to formyl peptide attractants in a dose-dependent manner. Half-maximal inhi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90204-3
更新日期:1988-02-01 00:00:00
abstract::Previously, we reported that the multidrug resistance proteins MRP1, MRP2 and MRP3 confer resistance to therapeutic antifolates by mediating their cellular extrusion. We now determined whether MRPs also play a role in controlling cellular homeostasis of natural folates. In MRP1, MRP2 and MRP3-transfected 2008 human ov...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01615-5
更新日期:2003-03-01 00:00:00
abstract::Stimulation of hepatic glycogenolysis and vasoconstriction of the hepatic vasculature in response to acetyl glyceryl ether phosphocholine (AGEPC; platelet activating factor) was inhibited by two structural analogues of AGEPC, U66985 (1-O-octadecyl-2-O-acetyl-sn-glycero-3-phosphoric acid-6'-trimethyl ammonium hexyl est...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90073-0
更新日期:1986-03-15 00:00:00
abstract::Triethylamine, which was used as an elution solvent for column chromatography to purify chemically synthesized 3'-phosphoadenosine 5'-phosphosulfate (PAPS), was a potent inhibitor of rat liver sulfotransferase (ST) activities toward androsterone and dehydroepiandrosterone, but not ST activities toward cortisol and 2-n...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90523-y
更新日期:1993-08-03 00:00:00
abstract::The characteristics of the muscarinic receptor in isolated gastric fundic cells from rabbit were determined by radioligand binding techniques and functional tests. The dissociation constants (KDS) of selective (hexahydrosiladifenidol and pirenzepine) and non-selective (N-methylscopolamine and atropine) muscarinic rece...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90209-7
更新日期:1987-09-15 00:00:00
abstract::After rats were injected with the reduced glutathione (GSH) depletor phorone (diisopropylidene acetone, 250 mg/kg, i.p.), there was a significant increase in microsomal glutathione S-transferase activity in the liver. The maximum activity was observed 24 hr after injection and was about 2-fold that of the control acti...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90216-9
更新日期:1986-02-01 00:00:00
abstract::The discovery of caspase activation counts as one of the most important finds in the biochemistry of apoptosis. However, targeted disruption of caspases does not impair every type of apoptosis. Other proteases can replace caspases and several so called "caspase independent" pathways are now described. Here we review o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2008.07.039
更新日期:2008-12-01 00:00:00
abstract::The mechanism by which p-chlorophenoxyisobutyric acid (clofibric acid) induces striking changes in the proportion of the molecular species of phosphatidylcholine (PC) in rat liver was studied. Treatment of rats with clofibric acid strikingly increased the content of 1-palmitoyl-2-oleoyl (16:0-18:1) PC, but decreased t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00735-3
更新日期:2001-10-01 00:00:00
abstract::Monocrotaline is a pyrrolizidine alkaloid obtained from the seeds of Crotalaria spectabilis. When perfused through an isolated liver, monocrotaline is metabolized to Ehrlich reactive (E+) metabolites. Metabolism of monocrotaline was faster in livers from male rats than female rats, was inducible with phenobarbital pre...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90721-4
更新日期:1984-08-01 00:00:00
abstract::Snake venom three-finger α-neurotoxins (α-3FNTx) act on postsynaptic nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction (NMJ) to produce skeletal muscle paralysis. The discovery of the archetypal α-bungarotoxin (α-BgTx), almost six decades ago, exponentially expanded our knowledge of membrane rec...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.114168
更新日期:2020-11-01 00:00:00
abstract::GABAB receptors assemble from GABAB1 and GABAB2 subunits. GABAB2 additionally associates with auxiliary KCTD subunits (named after their K(+) channel tetramerization-domain). GABAB receptors couple to heterotrimeric G-proteins and activate inwardly-rectifying K(+) channels through the βγ subunits released from the G-p...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.07.013
更新日期:2014-10-01 00:00:00
abstract::Duration of gene silencing due to the short-term silencing effects induced by exogenous siRNA have limited the therapeutic applications of RNAi and the development of RNAi-based therapeutics. We here generated Eg5 shRNA-expressing plasmids using the inverted terminal repeats (ITRs) sequences to produce Eg5 hairpin RNA...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.05.021
更新日期:2019-08-01 00:00:00
abstract::The chiral inversion properties of 4-(4-methylphenyl)-2-methylthiomethyl-4-oxobutanoic acid (KE-748), an active metabolite of 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298), were compared with those of ibuprofen in rats. After administration of R(-)-[2 alpha-2H]KE-748, S(+)-KE-748 was present in the...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00658-2
更新日期:1997-01-24 00:00:00
abstract::Mammary gland and liver microsomes of lactating rats were examined for the components of mixed function oxidase and related enzyme activities. Cytochrome b5, NADH- and NADPH- dependent cytochrome c reductase activities were 15-, 6- and 10-fold lower, respectively, in the mammary gland than in the liver microsomes. The...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90217-9
更新日期:1982-01-15 00:00:00
abstract::The vasoactive urotensin-II (UII), a cyclic undecapeptide widely distributed in cardiovascular, renal and endocrine systems, specifically binds the UII receptor (UT receptor), a G protein-coupled receptor (GPCR). The involvement of this receptor in numerous pathophysiological conditions including atherosclerosis, hear...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.08.023
更新日期:2014-11-15 00:00:00
abstract::To study the effect of sex hormones and alcohol on the hepatic activities of alcohol metabolizing enzymes, estradiol or testosterone were administered for 4 weeks to ovarectomized or sham operated adult female rats pair-fed nutritionally adequate liquid diets containing either alcohol (36% of total calories) or isocal...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90229-7
更新日期:1986-02-01 00:00:00
abstract::Multidrug resistance (MDR) is a phenomenon where cancer cells become simultaneously resistant to anticancer drugs with different structures and mechanisms of action. MDR has been shown to be associated with overexpression of ATP-binding cassette (ABC) transporters. Here, we report that telatinib, a small molecule tyro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.02.012
更新日期:2014-05-01 00:00:00
abstract::Certain anticonvulsant drugs require N-acetylation as a major route of metabolic clearance. Single point mutations of the polymorphic N-acetyltransferase gene (pNAT) are the primary cause for impaired drug acetylation. Pharmacokinetic parameters are altered in slow acetylator phenotypes and this may compromise drug sa...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90456-1
更新日期:1994-11-01 00:00:00
abstract::The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90045-7
更新日期:1991-07-25 00:00:00