Abstract:
:Nitric oxide (NO) shows tumoricidal activity. We had previously reported that NO downregulates the phosphatidylinositol-3-kinase/Akt pathway, but upregulates the MEK/ERK pathway downstream of growth factor signaling. We hypothesized that NO donor and MEK inhibitor in combination synergistically inhibit the viability of cancer cells compared to either NO donor or MEK inhibitor alone. We determined the effects of S-nitrosoglutathione (GSNO, NO-donor) and U0126 (MEK inhibitor) on insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) signaling, proliferation and invasion in cancer cell lines. GSNO inhibits phosphorylation of IGF-I receptor (IGF-IR), EGF receptor (EGFR) and Akt, but upregulates ERK1/2 phosphorylation in MIAPaCa-2 and HCT-116 cells after stimulation by IGF-I and EGF. On the other hand, U0126 inhibits phosphorylation of ERK1/2, but upregulates phosphorylation of IGF-IR and EGFR in MIAPaCa-2 and HCT-116 cells. The combination of GSNO and U0126 downregulates phosphorylation of IGF-IR, EGFR, Akt and ERK1/2 after stimulation by IGF-I and EGF. GSNO as well as U0126, inhibits the proliferation of MIAPaCa-2, HCT-116, Panc-1, MCF-7, HT-29 and AGS cells in a dose-dependent manner. GSNO and U0126 in combination synergistically inhibit proliferation and invasion of cancer cells. These results indicate that the combined treatment of NO donor and MEK inhibitor may be promising in cancer therapy.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Furuhashi S,Sugita H,Takamori H,Horino K,Nakahara O,Okabe H,Miyake K,Tanaka H,Beppu T,Baba Hdoi
10.3892/ijo.2011.1243subject
Has Abstractpub_date
2012-03-01 00:00:00pages
807-15issue
3eissn
1019-6439issn
1791-2423journal_volume
40pub_type
杂志文章abstract::The p16INK4a tumor suppressor gene is frequently inactivated in nasopharyngeal carcinoma (NPC) and hence it may play an important role in the suppression of this tumor. In order to study the effect of p16INK4a restoration in NPC cells, full-length human p16INK4a gene was transfected into a NPC cell line, CNE1. Four in...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract::Pancreatic cancer is one of the most aggressive solid malignancies with a dismal survival rate. Recent studies have shown that high expression levels of histone deacetylase 3 (HDAC3) correlate with malignant phenotype. However, the expression patterns and biological role of HDAC3 in pancreatic cancer remain unclear. I...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2568
更新日期:2014-10-01 00:00:00
abstract::Clinicopathological assessment of the functional relationship between the HER2 oncogene and tumor-associated fatty acid synthase (FASN) is largely precluded because immunohistochemical and/or mRNA studies should be performed in biopsies from breast cancer patients. We here sought to determine whether serum FASN (sFASN...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000455
更新日期:2009-12-01 00:00:00
abstract::The mutation of isocitrate dehydrogenase (IDH)1 (R132H) and IDH2 (R172K) and the induction of hypoxia in various solid tumors results in alterations in metabolic profiles, including the production of the d‑ or l‑forms of 2‑hydroxyglutarate (2HG) from α‑ketoglutarate in aerobic metabolism in the tricarboxylic acid (TCA...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4649
更新日期:2019-02-01 00:00:00
abstract::Human chondrosarcoma cells (HCS-TG) were transduced with the gene for a herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase (lacZ). We investigated the cytotoxicity of human chondrosarcoma bearing an HSV-tk gene after treatment with ganciclovir. Chondrosarcoma cells bearing an HSV-tk ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.14.6.1137
更新日期:1999-06-01 00:00:00
abstract::Sorafenib is currently used to treat advanced and/or unresectable hepatocellular carcinoma (HCC), but the increase of the median survival was only 3 months. Moreover, sorafenib has severe side effects and patients develop resistance quickly. Epigenetic alterations such as DNA methylation play a decisive role in the de...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.4019
更新日期:2017-07-01 00:00:00
abstract::The microtubule associated tumor suppressor gene 1 (MTUS1) is a recently published tumor suppressor gene, which has also been shown to act as an early component in the growth inhibitory signaling cascade of the angiotensin II type 2 receptor (AT2R). In this study we report the generation of MTUS1 knock-out (KO) mice, ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1311
更新日期:2012-04-01 00:00:00
abstract::Human breast cancer is a major cause of global morbidity and mortality in women and it is a process that involves numerous molecular and cellular alterations attributed to environmental substances and agents such as hormones. Bisphosphonates, such as pamidronate, are potent antiresorptive drugs used to the treatment o...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2955
更新日期:2015-01-01 00:00:00
abstract::Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many types of cell lines and tissues have demonstrated the presence of SP cells, including colon cancer cell lines. This study aimed to identify cancer stem cells (CSCs) in the SP of the colon cancer cell line SW480. SP c...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2498
更新日期:2014-09-01 00:00:00
abstract::Chemokine-mediated activation of G protein-coupled receptors CXCR1/2 promotes tumor growth, invasion, inflammation and metastasis. Repertaxin, a CXCR1/2 small-molecule inhibitor, has been shown to attenuate many of these tumor-associated processes. The present study aimed to investigate the effects of repertaxin alone...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3371
更新日期:2016-04-01 00:00:00
abstract::Metallothionein 3 (MT-3) has the ability to regulate the growth of nerve cells, but the significance of MT-3 expression outside the central nervous system and its participation in carcinogenesis have not yet been clarified. The aim of our study was to investigate the expression of MT-3 in ductal breast cancer and to d...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3759
更新日期:2016-12-01 00:00:00
abstract::The Pleomorphic adenoma gene 1 (PLAG1) is involved in various human neoplasias, including pleomorphic adenomas of the salivary glands. Moreover, the oncogenic role of PLAG1 was clearly demonstrated in two independent PLAG1 transgenic mouse founders, in which PLAG1 expression could be targeted to different tissues usin...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-05-01 00:00:00
abstract::Chemo- and radiotherapy induce apoptosis in tumours and surrounding tissues. In a search for robust and reliable apoptosis markers, we have evaluated immunostaining patterns of gammaH2AX and cleaved PARP-1 in paraffin-embedded cellular spheroids. Breast cancer BT474 cells were grown as cell spheroids to diameters of 7...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000311
更新日期:2009-07-01 00:00:00
abstract::Phosphorylation of histone H2AX (gammaH2AX) is a sensitive marker of DNA damage, particularly induction of DNA double-strand breaks. Using multiparameter cytometry we explored the effects of doxorubicin (DOX), cisplatin (CDDP) and 5-fluorouracil (5-FU) on four types of endometrioid adenocarcinoma cell lines (HEC-1A, H...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000589
更新日期:2010-05-01 00:00:00
abstract::We investigated the clinical significance of the expression levels of matrix metalloproteinase 9 (MMP-9) in renal cell carcinoma (RCC). In addition, we validated the efficacy of pyrrole imidazole polyamide (PIP) targeting MMP-9 on inhibiting proliferation and invasion of RCC. We evaluated the expression levels of MMP-...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2073
更新日期:2013-11-01 00:00:00
abstract::We performed interventional treatments on 50 patients with hepatocellular carcinoma (HCC) and analyzed the relationship between these treatments and the exacerbation of liver function after treatment. The different treatments included transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (P...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.19.6.1279
更新日期:2001-12-01 00:00:00
abstract::An altered expression of microRNAs (miRNAs) contributes both to the development of cancer and to the progression of the disease. Malignant tumours and tumour cell lines have widespread deregulated expressions of miRNAs compared to normal tissues. In this study, we investigated the expression profiles of 340 mammalian ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1420
更新日期:2012-07-01 00:00:00
abstract::Placenta-specific protein 1 (PLAC1) expression is co-opted in numerous human cancers. As a consequence of PLAC1 expression, tumor cells exhibit enhanced proliferation and invasiveness. This characteristic is associated with increased aggressiveness and worse patient outcomes. Recently, the presence of the tumor suppre...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.3931
更新日期:2017-05-01 00:00:00
abstract::There is emerging evidence for the prognostic role of various microRNA (miRNA) molecules in colon cancer. The aim of this study was therefore to compare the miRNA profiles in the primary tumor of patients with recurrent and non-recurrent colon cancer. The study population included 110 patients, 51 (46%) with stage I a...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1403
更新日期:2012-06-01 00:00:00
abstract::One of the genes that the authors have isolated by a differential display of hepatocellular carcinoma compared to adjacent liver is the alpha6 integrin. alpha6 integrin is the major adhesion receptor for laminin and is suggested to be involved in tumor cell invasion and metastasis. To our knowledge, however, there are...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.16.4.725
更新日期:2000-04-01 00:00:00
abstract::The hepatitis B virus (HBV) encodes a 16.5 kDa multifunctional protein termed pX or HBx, required for transcription of the viral genome and implicated in the development of hepatocellular carcinoma (HCC) in chronic HBV-infected patients. However, the mechanism of pX-mediated hepatocarcinogenesis remains unknown. pX is...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.15.2.373
更新日期:1999-08-01 00:00:00
abstract::Many clinical studies highlight the dichotomous role of PRDXs in human cancers, where they can exhibit strong tumor-suppressive or tumor-promoting functions. Recent evidence suggests that lower expression of PRDXs correlates with cancer progression in colorectal cancer (CRC) or in esophageal squamous carcinoma. In the...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2208
更新日期:2014-02-01 00:00:00
abstract::Protein disulfide‑isomerase A3 (PDIA3) is a chaperone protein that modulates folding of newly synthesized glycoproteins and responds to endoplasmic reticulum (ER) stress. Previous studies reported that increased expression of PDIA3 in hepatocellular carcinoma (HCC) is a marker for poor prognosis. However, the mechanis...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4710
更新日期:2019-04-01 00:00:00
abstract::The tumor suppressor gene product p53 has been detected in a high percentage of esophageal squamous cell carcinoma. To evaluate the role of this protein in carcinogenesis, we examined the p53 overexpression both in esophageal dysplasia and in esophageal squamous cell carcinoma in the same patients. Using anti-p53 anti...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.4.5.1061
更新日期:1994-05-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is associated with tumor malignancy. The hedgehog-EMT pathway is preferentially activated in diffuse-type gastric cancer (GC) compared with intestinal-type GC; however, histological typing is currently the only method for distinguishing these two major types of GC. We compared t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2387
更新日期:2014-06-01 00:00:00
abstract::Trophoblasts are derived from the normal placenta, and they infiltrate into the endometrium and the maternal blood vessels under strict control but, unlike malignant cells, never metastasize. To understand the proliferative characteristics of trophoblasts and its related disorders, we assessed telomerase activity in c...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.1.81
更新日期:1998-01-01 00:00:00
abstract::Metal-containing compounds have been extensively studied for many years as potent proteasome inhibitors. The 20S proteasome, the main component of the ubiquitin proteasome pathway, is one of the excellent targets in anticancer drug development. We recently reported that several copper complexes were able to inhibit ca...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3542
更新日期:2016-08-01 00:00:00
abstract::Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH) are Hedgehog family ligands, which play key roles in embryogenesis and carcinogenesis, especially in pancreatic cancer and gastric cancer. Drosophila Costal-2 (Cos2) is a Hedgehog signaling regulator, interacting with Smoothened (Smo), Cubitus inter...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract::Cordycepin is the main functional component of Cordyceps militaris, which has been widely used in oriental traditional medicine. This compound has been shown to possess many pharmacological properties, such as enhancing the body's immune function, and anti-inflammatory, anti-aging and anticancer effects. In the presen...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1762
更新日期:2013-03-01 00:00:00
abstract::We previously showed that the B cell leukemia cell line NALM-6 had the highest susceptibility among a number of leukemia cell lines to spiruchostatin B (SP-B), a potent histone deacetylase (HDAC) inhibitor. We also showed that SP-B-induced cytotoxicity depended on induction of apopt...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1507
更新日期:2012-09-01 00:00:00