Abstract:
:Background: Sorafenib (Nexavar®) is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S, a PKCδ activator, was selected as a potential candidate anticancer agent to be combined with sorafenib to promote the anti-cancer activity through synergistic interaction. Methods: The antitumor effects of sorafenib, OSU-2S and their combination were assessed by MTT assay, caspase activation, Western blotting, migration/invasion assays in four different HCC cell lines. The synergistic interactions were determined by Calcusyn analysis. PKCδ knockdown was used to elucidate the role of PKCδ activation as a mechanism for the synergy. The knockdown/over-expression of p53 was used to explain the differential sensitivity of HCC cell lines to sorafenib and/or OSU-2S. Results: OSU-2S synergistically enhanced the anti-proliferative effects of sorafenib in the four used HCC cell lines with combination indices <1. This effect was accompanied by parallel increases in caspase 3/7 activity, PARP cleavage, PKCδ activation and inhibition of HCC cell migration/invasion. In addition, PKCδ knockdown abolished the synergy between sorafenib and OSU-2S. Furthermore, p53 restoration in Hep3B cells through the over-expression rendered them more sensitive to both agents while p53 knockdown from HepG2 cells increased their resistance to both agents. Conclusion: OSU-2S augments the anti-proliferative effect of sorafenib in HCC cell lines, in part, through the activation of PKCδ. The p53 status in HCC cells predicts their sensitivity toward both sorafenib and OSU-2S. The proposed combination represents a therapeutically relevant approach that can lead to a new HCC therapeutic protocol.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Omar HA,Tolba MF,Hung JH,Al-Tel THdoi
10.3389/fphar.2016.00463subject
Has Abstractpub_date
2016-11-30 00:00:00pages
463issn
1663-9812journal_volume
7pub_type
杂志文章abstract::Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), are idiosyncratic and unpredictable drug-hypersensitivity reactions with a high-mortality rate ranging from 10% to over 30%, thus causing a...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00969
更新日期:2020-07-02 00:00:00
abstract::This study investigated the role of miR-3188 on the proliferation of non-small cell lung cancer cells and its relationship to FOXO1-modulated feedback loop. Two non-small cell lung cancer (NSCLC) cell lines A549 and H1299 were used. RNA silencing was achieved by lentiviral transfection. Cell proliferation was assessed...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01362
更新日期:2018-12-11 00:00:00
abstract::The ecto-5'-nucleotidase (ecto-5'NT/CD73) represents a crucial enzyme for endogenous adenosine generation. Several findings have shown that CD73 plays an important role in regulating vascular permeability and immune cell function. Adenosine 5'-(α,β-methylene)diphosphate (APCP) is a CD73 inhibitor, widely used as pharm...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00775
更新日期:2019-07-11 00:00:00
abstract::There are three members of the endogenous gas transmitter family. The first two are nitric oxide and carbon monoxide, and the third newly added member is hydrogen sulfide (H2S). They all have similar functions: relaxing blood vessels, smoothing muscles, and getting involved in the regulation of neuronal excitation, le...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00702
更新日期:2020-05-14 00:00:00
abstract::We have previously discovered a synergistically therapeutic combination of two Toll-like receptor ligands, an oligodeoxynucleotide (ODN) and Pam2CSK4. Aerosolization of these ligands stimulates innate immunity within the lungs to prevent pneumonia from bacterial and viral pathogens. Here we examined the safety and tol...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2014.00008
更新日期:2014-02-06 00:00:00
abstract::Nanomedicines can be used for a variety of cancer therapies including tumor-targeted drug delivery, hyperthermia, and photodynamic therapy. Poly (lactic-co-glycolic acid) (PLGA)-based materials are frequently used in such setups. This review article gives an overview of the properties of previously reported PLGA nanop...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.01260
更新日期:2018-11-02 00:00:00
abstract::Advances in molecular pathology have changed the landscape of oncology. The ability to interrogate tissue samples for oncogene amplification, driver mutations, and other molecular alterations provides clinicians with an enormous level of detail about their patient's cancer. In some cases, this information informs trea...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2016.00327
更新日期:2016-09-26 00:00:00
abstract::Novel therapeutic strategies for breast cancer are urgently needed due to the sustained development of drug resistance and tumor recurrence. Trivalent arsenic derivative (arsenite, AsIII) has been reported to induce cytotoxicity in breast cancer cells. We recently demonstrated that AsIII plus tetrandrine (Tetra), a Ch...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01087
更新日期:2020-07-17 00:00:00
abstract::Panax ginseng has been used as an herbal medicine for thousands of years. Most of its pharmacological effects are attributed to its constituent ginsenosides, including 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (20(S)-25-OCH3-PPD), which is one of the protopanaxadiol type ginsenosides. It has been found to exhibit ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00521
更新日期:2020-04-22 00:00:00
abstract::[This retracts the article on p. 15 in vol. 2, PMID: 21687510.]. ...
journal_title:Frontiers in pharmacology
pub_type: 撤回出版物
doi:10.3389/fphar.2014.00283
更新日期:2014-12-17 00:00:00
abstract:Background:Takotsubo syndrome (TTS) and acute coronary syndrome (ACS) patients have a similar mortality rate. In this study, we sought to determine the short- and long-term outcome of TTS patients as compared to ACS patients both treated with beta-blockers. Objectives:In the present study we described the data of 5 ye...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00681
更新日期:2020-05-14 00:00:00
abstract::Background: Genetic variability in some of the genes that affect absorption, distribution, metabolism, and elimination ("pharmacogenes") can significantly influence an individual's response to the drug and consequently the effectiveness of treatment and possible adverse drug events. The rapid development of sequencing...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00240
更新日期:2019-03-14 00:00:00
abstract::Objective: To evaluate therapeutic efficacy of different combined antimicrobial treatments against Acinetobacter baumannii ventilator-associated pneumonia (VAP). Methods: Clinical outcomes were retrospectively analyzed to elucidate the efficacy of four combined antimicrobial regimens. The chessboard and micro broth di...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00092
更新日期:2019-02-13 00:00:00
abstract:Objective:To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults. Methods:Multiple electronic databases were searched to find randomized controlled trials (RCTs) on paroxetine and panic disorder. The primary efficacy outcomes were: the mean change compared to the...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2020.00275
更新日期:2020-03-31 00:00:00
abstract::Pancreatic cancer decreases survival time and quality of life because of drug resistance and peripheral neuropathy during conventional treatment. This study was undertaken to investigate whether αvβ3 integrin receptor antagonist compounds NDAT and XT199 can suppress the development of cisplatin resistance and cisplati...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00095
更新日期:2020-02-27 00:00:00
abstract::Successful recovery from hepatectomy is partially contingent upon the rate of residual liver regeneration. The traditional Chinese medicines known as Periplaneta americana extracts (PAEs) positively influence wound healing by promoting tissue repair. However, the effect of PAEs on liver regeneration is unknown. We use...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01174
更新日期:2020-07-31 00:00:00
abstract::Hepatitis C virus, human immunodeficiency virus, and hepatitis B virus are chronic viral infections that cause considerable morbidity and mortality throughout the world. In the decades following the identification and sequencing of these viruses, in vitro experiments demonstrated that heme oxygenase-1, its oxidative p...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2012.00129
更新日期:2012-10-04 00:00:00
abstract::Paeoniflorin (PF) is the main active component of Paeonia lactiflora Pall., which is used in the treatment of severe cholestatic hepatitis. However, its biological mechanism in regulating bile acid metabolism and cholestatic liver injury has not been fully revealed. Our study aimed to reveal the mechanism of PF in the...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.586806
更新日期:2020-10-20 00:00:00
abstract::Xueshuantong Lyophilized Powder (XST), consisting of a series of saponins extracted from Panax notoginseng, is widely applied to treat acute cerebral infarction, stroke, and coronary heart disease in China. However, most adverse drug reactions (ADR) in clinic are caused by quality problems of XST. In this study, six b...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00633
更新日期:2018-06-15 00:00:00
abstract::The mTOR signaling pathway is abnormally activated in pancreatic cancer and is related to tumor glucose metabolism. However, its specific regulation mechanism is still unclear. Therefore, this study aims to investigate whether Sestrin2 affects the glucose metabolism of pancreatic cancer by modulating mTOR signal and t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.580407
更新日期:2020-11-11 00:00:00
abstract::A better understanding of the negative impact of general anesthetics on gastrointestinal motility requires thorough knowledge of their molecular targets. In this respect the muscarinic cationic current (mICAT carried mainly via TRPC4 channels) that initiates cholinergic excitation-contraction coupling in the gut is of...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.594882
更新日期:2020-12-18 00:00:00
abstract:Background:Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the prote...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01257
更新日期:2020-08-12 00:00:00
abstract:AIMS:Myocardial ischemia can result in marked mitochondrial damage leading to cardiac dysfunction, as such identifying novel mechanisms to limit mitochondrial injury is important. This study investigated the hypothesis that inhibiting soluble epoxide hydrolase (sEH), responsible for converting epoxyeicosatrienoic acids...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00133
更新日期:2016-06-07 00:00:00
abstract::Background: Up to date, the efficacy and safety of warfarin treatment in atrial fibrillation patients receiving hemodialysis remain controversial. So we performed this meta-analysis to try to offer recommendations regarding warfarin management in this population. Methods: We searched Pubmed, Embase, and Cochrane libra...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01218
更新日期:2018-11-06 00:00:00
abstract::Objective: San-Cao granule (SCG), a traditional Chinese herb formula, has been used for treating autoimmune hepatitis (AIH) in our clinics for a long time. However, its active ingredients and mechanisms of action were still unknown due to its complicated chemical compositions. In the present study, the pharmacological...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00624
更新日期:2018-06-12 00:00:00
abstract::Most breast and prostate tumors are hormone-dependent, making it possible to use hormone therapy in patients with these tumors. The design of effective endocrine drugs that block the growth of tumors and have no severe side effects is a challenge. Thereupon, synthetic steroids are promising therapeutic drugs for the t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00979
更新日期:2018-01-10 00:00:00
abstract:BACKGROUND:The dried root of Paeonia lactiflora Pall. (PLP) is a classical Chinese herbal medicine that has been used to treat hepatic disease for 1000s of years. Our previous work suggested that PLP can be used to treat hepatitis with severe cholestasis. This study explored the mechanism by which PLP affects ANIT-indu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00014
更新日期:2016-02-04 00:00:00
abstract::Objective: The aim of the present study was to encapsulate vancomycin in different liposomal formulations and compare the in vitro antimicrobial activity against Staphylococcus aureus biofilms. Methods: Large unilamellar vesicles of conventional (LUV VAN), fusogenic (LUVfuso VAN), and cationic (LUVcat VAN) liposomes e...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01401
更新日期:2019-11-29 00:00:00
abstract::The Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) or novel coronavirus (COVID-19) infection has been declared world pandemic causing a worrisome number of deaths, especially among vulnerable citizens, in 209 countries around the world. Although several therapeutic molecules are being tested, no ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.01189
更新日期:2020-08-07 00:00:00
abstract::Despite improvements in early diagnosis and treatment, breast cancer is still a major health problem worldwide. Among breast cancer subtypes, the most challenging and harder to treat is represented by triple-negative molecular subtype. Due to its intrinsic features this subtype cannot be treated neither with hormonal ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00725
更新日期:2020-05-20 00:00:00