Abstract：
BACKGROUND:Sorafenib is an oral multi-kinase inhibitor that inhibits hepatocellular carcinoma (HCC) via the Ras/Raf/MAPK pathway. However, sorafenib loses effectiveness because most tumors acquire drug resistance over time. As the PI3K/AKT/mTOR signaling pathway is also activated abnormally in HCC, we evaluated the effect of sorafenib, in combination with a dual PI3K/mTOR inhibitor, BEZ235, on HCC cell proliferation and survival in vitro. MATERIALS AND METHODS:Biological phenotypes were analysed in HCC cell lines, parental and sorafenib-resistant HepG2 cells (HepG2 and HepG2R), treated with sorafenib or BEZ235, alone or in combination. HCC cellular proliferation and apoptosis were investigated, and perturbations of the Ras/Raf/MAPK and PI3K/AKT/mTOR signaling/survival pathways were evaluated by western blot analysis. RESULTS:BEZ235 enhanced sorafenib inhibition of cellular proliferation, migration, and promotion of apoptosis in HepG2 and HepG2R cells. The combined effects were associated with inhibition of phosphorylation of AKT, mTOR and S6K in the PI3K/AKT/mTOR pathway, whereas the combination of sorafenib and BEZ235 did not significantly alter the Ras/Raf/MAPK pathway compared with the effect of sorafenib alone. CONCLUSION:Sorafenib/BEZ235 combination has potent anti-HCC cell activity. This anti-tumor activity is most likely multi-factorial, mainly involving PI3K down-regulation and AKT, mTOR and S6K dephosphorylation. Combined inhibition of PI3K/AKT/mTOR and Ras/Raf/MAPK pathways enhances sorafenib inhibition of HCC. The results of these in vitro studies suggest that trials of combined sorafenib and BEZ235 in the treatment of HCC should be considered.
journal_name
Am J Transl Resjournal_title
American journal of translational researchauthors
Li A,Zhang R,Zhang Y,Liu X,Wang R,Liu J,Liu X,Xie Y,Cao W,Xu R,Ma Y,Cai W,Wu B,Cai S,Tang Xsubject
Has Abstractpub_date
2019-09-15 00:00:00pages
5573-5585issue
9issn
1943-8141journal_volume
11pub_type
杂志文章abstract：:The microRNA-29 family, which contains mir-29a, mir-29b, and mir-29c, can promote or resist the development of several types of tumors. However, its role in rhabdomyosarcoma (RMS) has not been determined. In this work, we detected the expression of mir-29a/b/c in RMS. Results showed that the tissues and cell lines in ...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2020-03-15 00:00:00
abstract：:The histone deacetylase inhibitors, suberoylanilide hydroxamic acid (Vorinostat, Zolinza™) and depsipeptide (Romidepsin, Istodax™) have been approved by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Numerous histone deacetylase inhibitors are currently undergoing clinic...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2012-01-01 00:00:00
abstract：:Isoflurane (ISO) exhibits neuroprotective effects against inflammation and apoptosis. However, the role of ISO in motoneuronal apoptosis induced by activated microglia remains poorly studied. We investigated the protective effects of ISO on the apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons induced by lipop...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2016-03-15 00:00:00
abstract：OBJECTIVE:To create the rabbit animal model of intervertebral disc (IVD) degeneration by the annulus needle puncture technique through a novel transabdominal approach. METHODS:Thirteen New Zealand White rabbits underwent annular puncture at the L3/4, L4/5, and L5/6 discs through a transabdominal approach. For a longit...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2017-03-15 00:00:00
abstract：BACKGROUND:There is conflicting evidence regarding the prognostic value of cytotoxic T cell infiltration in breast cancer. The aims of this study were to detect the expression levels and localization of FoxP3 and CD8 in invasive ductal carcinoma of the breast and to investigate the correlations among FoxP3+ regulatory ...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2019-08-15 00:00:00
abstract：:Current knowledge of normal developmental physiology and identification of specific cell types of the kidney at molecular levels enables us to generate various cells of the kidney. The generation of renal specialized cells in vitro with its correct molecular and functional implications is the urgent need for cellular ...
journal_title：American journal of translational research
pub_type： 杂志文章,评审
doi：
更新日期：2019-02-15 00:00:00
abstract：:Observational research suggests that exercise may reduce the risk of breast cancer and improve survival. One proposed mechanism for the protective effect of aerobic exercise related to cancer risk and outcomes, but has not been examined definitively, is the immune response to aerobic exercise. Two prevailing paradigms...
journal_title：American journal of translational research
pub_type： 杂志文章,评审
doi：
更新日期：2014-10-11 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2009-07-15 00:00:00
abstract：BACKGROUND:Circular RNAs (circRNAs) represent a class of non-coding RNAs that are emerging as important regulators during tumorigenesis and provide potential targets for cancer intervention. However, the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC) have not been completely clarified. ...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2018-06-15 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2020-10-15 00:00:00
abstract：BACKGROUND:The cardioprotection of ischemic post-conditioning (IPO) has been well demonstrated after a short period of reperfusion. However, little is known about the long-term effects of IPO. This study aimed to investigate the long term cardioprotection of IPO in a rat myocardial ischemia/reperfusion model and to exp...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2015-12-15 00:00:00
abstract：:Circular RNAs (circRNAs), a new star noncoding RNA (ncRNA), show stability, conservation, abundance, and tissue and stage specificity. They act as key regulators of biological processes. They target the mRNAs of many other different genes or signaling pathways, and closely link associated genes into regulatory network...
journal_title：American journal of translational research
pub_type： 杂志文章,评审
doi：
更新日期：2020-05-15 00:00:00
abstract：:Gonadal hormones have been well-known to affect brain regions known to be involved in the modulation of mood and affective-related behavior. Prenatal stress might alter hypothalamic-pituitary-gonadal axis, it could be a target for development of affective-related disorders in male offspring. The present study was desi...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2017-03-15 00:00:00
abstract：:This study sought to determine the effect and explore the mechanism of the Chinese medicinal compound preparation Diwu Yanggan (DWYG) capsule on the occurrence and development of liver cancer using the Solt-Farber rat model. Sprague-Dawley rats were randomly distributed into a normal group, sham group, DWYG group, sor...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2018-11-15 00:00:00
abstract：BACKGROUND:Annexin A1 was investigated as prognostic factor because of its apparent association with tumorigenesis. The aim of this study was to investigate the expression of annexin A1 in lung cancer patients, and analysed the relationship with respect to the clinico-pathological features and assessed whether annexin ...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2014-10-11 00:00:00
abstract：:The clinical efficacy of PD-1/PD-L1 monoclonal antibodies (mAbs) in triple-negative breast cancer (TNBC) is unsatisfactory. Immunotherapy combined with chemotherapy shows good therapeutic potential. Preclinical and clinical studies have shown that metronomic chemotherapy may stimulate anticancer immune responses. We a...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2020-02-15 00:00:00
abstract：:Accumulating evidence suggests that brain metabolic changes may be associated with the pathophysiology of schizophrenia. Both in vivo and in vitro studies have found glutamatergic and GABAergic abnormalities in different brain regions of individuals with schizophrenia. We report a longitudinal behavioral study in a me...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2019-09-15 00:00:00
abstract：:Glioma-associated oncogene homolog 1 (GLI1), an oncogenic molecule in non-small cell lung cancer (NSCLC), promotes the growth of NSCLC by enhancing lung cancer stem cells (LCSCs). However, the mechanism responsible remains unknown. FOXP3 is known to maintain LCSCs. The aim of this study was to explore whether GLI1 enh...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2020-05-15 00:00:00
abstract：:Postoperative fever is prevalent in many breast cancer patients. Some retrospective studies proposed that postoperative fever might also be considered as a rapid rough indicator for the poor prognosis of breast cancer patients. This study aims to explore the possible molecular mechanisms underlying the relapse of brea...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2018-10-15 00:00:00
abstract：BACKGROUND:Glioma is the most common malignant tumor in the adult human brain and has one of the lowest patient survival rates. MicroRNAs (miRNAs) play important roles in the development of cancers, including glioma, and potentially have valuable therapeutic applications in glioma; however, their specific functions and...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2018-09-15 00:00:00
abstract：:Curcumin is a safe, cost-effective natural agent with multiple targets that displays therapeutic potential in cancer. Recently, we reported a novel curcumin analog, Da0324, which exhibited significantly improved stability and anti-cancer activity. However, the molecular mechanism underlying the anti-cancer activity of...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2020-07-15 00:00:00
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journal_title：American journal of translational research
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doi：
更新日期：2017-09-15 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2020-12-15 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2017-03-15 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2010-06-10 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2016-12-15 00:00:00
abstract：:MicroRNAs (miRNAs) are small regulatory non-coding RNAs that have been reported to play an important role in the tumorigenesis of many cancers. In addition, miRNAs might serve as new promising biomarkers for diagnosis and prognosis and as effective therapeutic targets for patients with such malignancies. Accordingly, ...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2020-03-15 00:00:00
abstract：:MTSS1 is a possible metastasis suppressor which has been proved to play a key role in metastasis of various tumors, yet its role in intrahepatic cholangiocarcinoma (ICC) remains unclear. In present study, we reported detection of MTSS1 expression in ICC and explored its clinical significances. Tissue microarrays conta...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2015-10-15 00:00:00
abstract：:Till now, no functional studies for FGF-16 in diabetic heart have been reported. Therefore, this study aims to evaluate the potential function of FGF-16 in inhibiting adverse cardiac remodeling in post myocardial infarction (MI) of diabetic heart. We investigated the role of fibroblast growth factor-16 (FGF-16) in pos...
journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2017-04-15 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2017-11-15 00:00:00
