Abstract：
:Glioma is a kind of lethal malignant tumor, and lacks efficient therapies. Combination therapy has been claimed to be a promising approach to combat cancer, due to its increased anti-cancer effects and reduced side effects. This study aimed to investigate the anti-cancer effect and mechanism of combining imatinib with irinotecan or its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). First, we found that this drug combination exerted synergistic antitumor effects against glioma in vitro and in vivo. In addition, flow cytometry results proved that the SN-38-induced apoptosis was further enhanced by imatinib, and similar results were observed by determining the protein expression levels of apoptosis biomarkers. Interestingly, p53 expression was elevated by the SN-38 mono-treatment, and was not further increased after the co-treatment; besides, knockdown of p53 could only reduce the expression of cleaved-PARP partially, and weaken the enhanced proliferation inhibition induced by SN-38 plus imatinib, indicating that there might be other factors involved in the synergistic effects besides p53. Meanwhile, the markedly elevated p21 expression was observed only in the combination group, instead of the mono-treated groups. According to the results of p21 knockdown, we found that p21 was also required for the synergistic inhibitory effects. Moreover, we explored and ruled out the possibility of imatinib enhancing the sensitivity of irinotecan by inhibiting drug efflux pumps. Thus, our findings collectively suggest that combining irinotecan with imatinib could be a promising new strategy to fight against glioma.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Lu J,Hu Y,Qian R,Zhang Y,Yang X,Luo Pdoi
10.1016/j.ejphar.2020.173022subject
Has Abstractpub_date
2020-05-05 00:00:00pages
173022eissn
0014-2999issn
1879-0712pii
S0014-2999(20)30114-Xjournal_volume
874pub_type
杂志文章abstract：:Leukotriene C4 binding to mouse brain membranes was readily displaced by S-alkylglutathione derivatives, with the affinity of the test compound increasing as the alkyl chain length increases. S-decylglutathione was as potent as leukotriene C4. These data suggest that brain membrane leukotriene C4 binding sites are S-a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90186-6
更新日期：1989-02-14 00:00:00
abstract：:With some latency, ouabain (10(-6)--10(-5) M) induced a long-lasting contractile response of the isolated vas deferens of the guinea-pig. The ouabain-induced contraction was potentiated by pretreatment with tropolone, whereas it was prevented by pretreatment with cocaine, bretylium, reserpine or phentolamine. The resp...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90121-8
更新日期：1978-02-15 00:00:00
abstract：:In neutrophils and several other phagocytes, a pertussis and cholera toxin-sensitive guanine nucleotide-binding protein (G-protein) couples the receptors for formyl methionine-containing chemotactic peptides to stimulation of phospholipase C. We used membranes of myeloid-differentiated HL 60 cells to study the role of...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(89)90031-x
更新日期：1989-12-05 00:00:00
abstract：:Substance P (SP) caused an immediate and vigorous contraction of the longitudinal smooth muscle layer of the guinea-pig ileum. The contractile response to SP, unlike that to acetylcholine or histamine was not maintained but faded to baseline levels in about 6 min. When 0.3-1.0 nM SP was added the fading time was short...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90597-0
更新日期：1982-06-16 00:00:00
abstract：:Trans-dehydrocrotonin has antiulcerogenic and antitumor activities. A complex of beta-cyclodextrin with dehydrocrotonin was developed to improve the delivery of dehydrocrotonin. Complex in solid state was evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TG...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.01.016
更新日期：2005-03-07 00:00:00
abstract：:To define the vasorelaxation mechanism of FK409, we examined the effect of the compound on vascular tension and cyclic nucleotide levels in isolated rat thoracic aorta contracted with norepinephrine, and on activities of guanylate cyclase and cyclic GMP phosphodiesterase prepared from rat or rabbit thoracic aorta. FK4...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(93)90032-5
更新日期：1993-08-15 00:00:00
abstract：:Platelet serotonin (5HT) uptake was measured in 18 subjects administered physostigmine salicylate in a double-blind, placebo crossover design. In comparison to placebo, the drug caused a significant transient depression in mood, as measured by self- and observer-rated depression scores. In addition, physostigmine sign...
journal_title：European journal of pharmacology
pub_type： 临床试验,杂志文章
doi：10.1016/0014-2999(85)90543-6
更新日期：1985-02-12 00:00:00
abstract：:Canine cerebral arterial strips denuded of endothelium responded to nicotine and transmural electrical stimulation with relaxations, which were abolished by NG-nitro-L-arginine and methylene blue. Magnitudes of relaxation did not differ in the arteries contracted with prostaglandin F2alpha and sumatriptan, an effectiv...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01019-6
更新日期：2001-05-18 00:00:00
abstract：:HgCl2 and mersalyl increased and later decreased both the spontaneous and evoked transmitter liberation at the frog neuromuscular junction. Lower concentration of HgCl2 exhibited only an inhibitory effect on transmitter release. These mercurials inhibited calcium transport of mitochondria and synaptosomal vesicles. Lo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90438-7
更新日期：1978-10-15 00:00:00
abstract：:Paclitaxel, an antitumoral drug, was used in a single dose (29 mg/kg i.p.) as an injury agent for inducing transient suppression of hematopoiesis in a murine experimental model during 10days. The aim of this study focuses on erythropoietin (EPO) receptor, GATA binding protein 1 (globin transcription factor 1) (GATA-1)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.02.056
更新日期：2010-06-25 00:00:00
abstract：:The effects of cannabinoid drugs on cAMP production were examined in mammalian brain. The cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3,-d,e-1,4-benzoxazin-6-yl]-(1-naphthalenyl) methanone (WIN55,212-2) decreased forskolin-induced cAMP accumulation in a concentration...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)01575-3
更新日期：2002-05-17 00:00:00
abstract：:To investigate the role of ATP-sensitive K+(KATP) channels on pacemaker activity in interstitial cells of Cajal (ICC), whole-cell patch clamping, RT-PCR, and intracellular Ca2+([Ca2+]i) imaging were performed in cultured colonic ICC. Pinacidil (a K+ channel opener) hyperpolarized the membrane and inhibited the generat...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.05.029
更新日期：2017-08-15 00:00:00
abstract：:After incubation of rat cortical cell cultures with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 12 h, cells showed fragmentation of DNA at internucleosomal linkers, the characteristic feature of apoptosis. In a quantitative approach, it was determined that the percentage of DNA fragmentation...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(92)90063-2
更新日期：1992-07-01 00:00:00
abstract：:Disturbances in oxidative metabolism are involved in many acute and chronic diseases, as well as in several other conditions. The objective of the present study was to examine the relationship between the level of intracellular reactive oxygen species in the peripheral blood granulocytes of mice, as evaluated by 2',7'...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.11.001
更新日期：2010-02-10 00:00:00
abstract：:Lipids and lipoproteins play a vital role in the pathogenesis of myocardial infarction. There are no studies reported on the protective effects of sinapic acid on changes in electrocardiogram, lipids and lipoproteins in myocardial infarction. This study aims to evaluate the protective effects of sinapic acid on cardia...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.11.012
更新日期：2013-01-15 00:00:00
abstract：:5-HT(1A) receptor activation by the very-high-efficacy, selective 5-HT(1A) receptor agonist F 13640 [(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-([(5-methyl-pyridin-2-ylmethyl)-amino]-methyl)piperidin-1-yl]-methanone] was recently discovered to constitute a novel central mechanism of broad-spectrum analgesia that, remarkab...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01566-8
更新日期：2003-04-18 00:00:00
abstract：:We compared the cumulative dose-response relations of verapamil (0.1, 0.2 and 0.4 mg kg(-1)) in different R/S enantiomer ratios (100/0, 90/10, 80/20, 50/50 and 20/80) on the electrophysiological and hemodynamic characteristics of the heart using the conscious dogs. A reduction of mean arterial pressure occurred with 2...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00480-4
更新日期：1998-08-21 00:00:00
abstract：:The role of leukotriene synthesis in the gastrointestinal damage induced by platelet-activating factor (PAF) was examined in the rat. The effects of a 20-min infusion of PAF (100 ng/kg per min) on leukotriene B4 (LTB4) and leukotriene C4 (LTC4) synthesis were examined in samples of the stomach, duodenum, jejunum, ileu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90690-5
更新日期：1988-06-22 00:00:00
abstract：:We evaluated the inotropic actions of levosimendan and epinephrine, both singly and in combination, under isohydric (pH 7.4) and acidotic (pH 7.0) conditions in isolated guinea-pig hearts. Acidosis depressed contractility and myocardial relaxation by 25-30%, and both inotropes were less efficacious at pH 7.0, while th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.11.049
更新日期：2005-01-10 00:00:00
abstract：:Large airway bronchoconstriction acts mainly through cholinergic pathways via muscarinic M3 receptors with some contribution from M2 receptors. By contrast, the mechanisms of small airway contraction are largely unknown. This study used precision cut lung slices to examine the role of muscarinic M2 and M3 receptors in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.01.054
更新日期：2013-02-28 00:00:00
abstract：:The insulin-like growth factor-1 receptor (IGF-1 receptor) is a receptor tyrosine kinase, highly homologous to the insulin receptor. In contrast to the insulin receptor, which is mostly involved in metabolic pathways, the IGF-1 system plays a pivotal role in normal and neoplastic cell growth through anti-apoptotic, pr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.01.052
更新日期：2007-05-07 00:00:00
abstract：:The quantitative [14C]2-deoxyglucose autoradiographic technique was applied to the measurement of the cerebral metabolic effects of adenosine A1 and A2 receptor agonists and antagonists in adult rats. The adenosine A1 receptor agonist and antagonist, 2-chloro-N6-cyclopentyladenosine (CCPA) and 8-cyclopentyl-1,3-diprop...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90057-4
更新日期：1994-06-02 00:00:00
abstract：:A recent study indicates that elevation of [Ca(2+)](i) enhances the release of calcein, an anionic fluorescent dye, from isolated exocrine acinar cells, so cytoplasmic calcein is useful for monitoring the secretion of organic anions. In this study, we investigated the effect of cAMP on the calcein release evoked by el...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00898-5
更新日期：2000-02-04 00:00:00
abstract：:Clinical use of gentamicin over prolonged periods is limited because of dose- and time-dependent nephrotoxicity. Primarily, lysosomal phospholipidosis, intracellular oxidative stress and heightened inflammation have been implicated. Hydrogen sulphide is an endogenously produced signal transduction molecule with strong...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.04.030
更新日期：2012-06-15 00:00:00
abstract：:The beta 1- and beta 2-adrenoceptor agonist and thromboxane A2 (TXA2) antagonist properties of trimetoquinol (TMQ, I) and 1-benzyl substituted TMQ analogues [3'-iodo-4',5'-dimethoxy TMQ, II; 3',5'-diiodo-4'-dimethoxy TMQ, III; 3',4'-dimethoxy-5'-nitro TMQ, IV; 3',4'-dimethoxy-5'-amino TMQ; V; and 3',4'-dimethoxy TMQ, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90663-q
更新日期：1990-08-02 00:00:00
abstract：:Excessive intracellular accumulation of zinc (Zn(2+)) is neurotoxic and contributes to a number of neuropathological conditions. Here, we investigated the protective effect of 3-morpholinosydnonimine (SIN-1) against Zn(2+)-induced neuronal cell death in differentiated PC12 cells. We found that Zn(2+)-induced PC12 cell...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.12.003
更新日期：2015-02-05 00:00:00
abstract：:The cellular mechanisms underlying the inhibitory effects of phenylephrine on dihydropyridine-sensitive, voltage-dependent Ca2+ currents recorded from single smooth muscle cells dissociated from the rat anococcygeus muscle were examined. Phenylephrine (0.1-30 microM) produced a concentration-dependent inhibition of th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(95)90049-7
更新日期：1995-02-15 00:00:00
abstract：:Substituted benzamides such as metoclopramide, cisapride, zacopride, renzapride or BRL 20627, stimulate intestinal motility in various species. As they are antagonists at 5-HT3 and agonists at 5-HT4 receptors and as both mechanisms could potentially contribute to their gastrointestinal prokinetic effect, the underlyin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90821-7
更新日期：1991-11-26 00:00:00
abstract：:Melatonin is of considerable interest for its regulatory influence on a variety of physiological processes including biological rhythms and neuroendocrine functions. We showed that melatonin potentiates sympathetic neurotransmission in the prostatic portion of the rat vas deferens, by increasing contractions in respon...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90696-3
更新日期：1994-05-12 00:00:00
abstract：:The effect of the kappa-opioid receptor agonist, bremazocine, on plasma oxytocin levels in rats was measured by a sensitive radioimmunoassay. Initially, a decrease in plasma oxytocin levels was seen 30 min after injection. This was in accordance with the bremazocine inhibition of oxytocin release after submaximal elec...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90681-x
更新日期：1989-07-04 00:00:00
