Downregulation of tetrahydrobiopterin inhibits tumor angiogenesis in BALB/c-nu mice with hepatocellular carcinoma.

Abstract:

:Hepatocellular carcinoma (HCC) is a highly vascular tumor, and treatment options for patients of advanced-stage are limited. Nitric oxide (NO), which is derived from endothelial nitric oxide synthase (eNOS), provides crucial signals for angiogenesis in the tumor microenvironment. Tetrahydrobiopterin (BH4) is an essential cofactor eNOS and represents a critical determinant of NO production. To examine whether treatment of 2,4-diamino-6-hydroxypyrimidine (DAHP) inhibits angiogenesis of HCC, BALB/c-nu mice were injected with HepG-2 cells with DAHP. Supplemental DAHP treatment decreased K-ras mRNA transcripts, inhibition of phosphorylation of eNOS and Akt, inhibition of guanosine triphosphate cyclohydrolase (GTPCH), and decreased significantly NO synthesis, and then inhibited angiogenesis, compared with the results observed in the saline group. Histopathology demonstrated angiogenesis and tumor formation were significantly inhibited in HCC. DAHP downregulates GTPCH protein expression, corresponding to decreased levels of BH4 and the contents of NO. In addition, DAHP downregulates eNOS and Akt protein expression, corresponding to decreased eNOS phosphorylation at Ser1177 and Akt phosphorylation, compared with the saline control. We suggest that DAHP, recognized as a specific competitive inhibitor of GTPCH, can decrease tumor BH4 and NO by the inhibition of the wild-type Ras-PI3K/Akt pathway, and then inhibiting angiogenesis, and may provide a novel and promising way to target BH4 synthetic pathways to inhibit angiogenesis and to control potential progression of HCC. Whether DAHP has a therapeutic potential will require more direct testing in humans.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Dai Y,Cui J,Gan P,Li W

doi

10.3892/or.2016.4850

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

669-75

issue

2

eissn

1021-335X

issn

1791-2431

journal_volume

36

pub_type

杂志文章
  • Increased numbers of endothelial progenitor cells in peripheral blood and tumor specimens in non-small cell lung cancer: a methodological challenge and an ongoing debate on the clinical relevance.

    abstract::Bone marrow-derived endothelial progenitor cells (EPC) play an important role in neovascularisation and tumor growth. However, the clinical relevance of EPCs on blood vessel formation in non-small cell lung cancer (NSCLC) is unclear. EPC numbers in circulation are very low and therefore their detection is technically ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Pircher A,Kähler CM,Skvortsov S,Dlaska M,Kawaguchi G,Schmid T,Gunsilius E,Hilbe W

    更新日期:2008-02-01 00:00:00

  • Atorvastatin partially inhibits the epithelial-mesenchymal transition in A549 cells induced by TGF-β1 by attenuating the upregulation of SphK1.

    abstract::Statins are the most effective drugs used in the reduction of intracellular synthesis of cholesterol. Numerous studies have confirmed that statins reduce the risk of multiple types of cancers. Statin use in cancer patients is associated with reduced cancer-related mortality. Epithelial-to-mesenchymal transition (EMT),...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4897

    authors: Fan Z,Jiang H,Wang Z,Qu J

    更新日期:2016-08-01 00:00:00

  • Gut-derived serotonin induced by depression promotes breast cancer bone metastasis through the RUNX2/PTHrP/RANKL pathway in mice.

    abstract::Breast cancer metastasizes to the bone in a majority of patients with advanced disease resulting in bone destruction. The underlying mechanisms are complex, and both processes are controlled by an interaction between locally and systemically derived signals. Clinically, breast cancer patients with depression have a hi...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4430

    authors: Zong JC,Wang X,Zhou X,Wang C,Chen L,Yin LJ,He BC,Deng ZL

    更新日期:2016-02-01 00:00:00

  • Knockdown of Bmi1 inhibits the stemness properties and tumorigenicity of human bladder cancer stem cell-like side population cells.

    abstract::B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) is directly involved in cell growth, proliferation and self-renewal of cancer stem cells (CSCs). The aim of the present study was to assess the role of Bmi1 in the maintenance of stemness properties and tumorigenicity of human bladder CSC-like side ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2919

    authors: Zhu D,Wan X,Huang H,Chen X,Liang W,Zhao F,Lin T,Han J,Xie W

    更新日期:2014-02-01 00:00:00

  • A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer.

    abstract::Insulin-like growth factor (IGF)-mediated signaling is a newly recognized clinical target in prostate cancer, and it is hypothesized that blockade of the IGF receptor (IGF1R) will impair downstream signaling and slow tumor growth. In this study the efficacy of nordihydroguaiaretic a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1487

    authors: Friedlander TW,Weinberg VK,Huang Y,Mi JT,Formaker CG,Small EJ,Harzstark AL,Lin AM,Fong L,Ryan CJ

    更新日期:2012-01-01 00:00:00

  • Involvement of TMEM22 overexpression in the growth of renal cell carcinoma cells.

    abstract::In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for development of novel treatments of renal cell carcinoma (RCC), we previously analyzed genome-wide gene expression profiles of clear-cell types of RCC by cDNA microarray. Among the transcativated genes, w...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Dobashi S,Katagiri T,Hirota E,Ashida S,Daigo Y,Shuin T,Fujioka T,Miki T,Nakamura Y

    更新日期:2009-02-01 00:00:00

  • Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT.

    abstract::Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid carcinoma with a poor prognosis. Thus, suitable preclinical tumor models are required for the development of new ATC therapies. In the present study, orthotopic tumor xenograft models were established using ATC cell lines and SCID mice, and tumor invasion an...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7720

    authors: Aoyama M,Takizawa H,Otani T,Inoue S,Kawakita N,Tsuboi M,Bando Y,Uehara H,Kondo K,Tangoku A

    更新日期:2020-10-01 00:00:00

  • Antitumor activity of monomethoxy poly(ethylene glycol)-poly (ε-caprolactone) micelle-encapsulated doxorubicin against mouse melanoma.

    abstract::Doxorubicin (Dox) is one of the most commonly used and highly effective antineoplastic agents, but the clinical application of this broad spectrum drug is largely hampered by its poor stability and serious toxicity to normal tissues. Hence, it is essential to improve the therapeutic effect and decrease the systematic ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1243

    authors: Zheng L,Gou M,Zhou S,Yi T,Zhong Q,Li Z,He X,Chen X,Zhou L,Wei Y,Qian Z,Zhao X

    更新日期:2011-06-01 00:00:00

  • Upregulated NOX1 expression in gallbladder cancer‑associated fibroblasts predicts a poor prognosis.

    abstract::Gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm of the biliary tract. Potential prognostic markers and therapeutic targets for this disease are urgently required. Cancer‑associated fibroblasts (CAFs) play a key role in tumorigenesis and the development of cancer. Nicotinamide adenine dinucleotide ph...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7249

    authors: Wang FT,Hassan M,Ansari KH,Xu GL,Li XP,Fan YZ

    更新日期:2019-10-01 00:00:00

  • Induction and mechanism of HeLa cell apoptosis by 9-oxo‑10, 11-dehydroageraphorone from Eupatorium adenophorum.

    abstract::9-Oxo-10, 11-dehydroageraphorone (euptox A), a cadenine sesquiterpene, is the main toxin from Eupatorium adenophorum. The aim of the present study was to examine the induction and mechanism of HeLa cell apoptosis by euptox A. The apoptosis‑inducing effect of the euptox A on HeLa cells was examined by MTT assay. The un...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.3778

    authors: Liao F,Hu Y,Wu L,Tan H,Luo B,He Y,Qiao Y,Mo Q,Wang Y,Zuo Z,Deng J,Wei Y

    更新日期:2015-04-01 00:00:00

  • Expression spectra of matrix metalloproteinases in metastatic non-small cell lung cancer.

    abstract::By combining suppression subtractive hybridization and microarray to examine gene expressions between metastatic and non-metastatic non-small cell lung cancer (NSCLC), we have identified differential expression spectra of matrix metalloproteinases (MMP). Among MMPs, expressions of MMP-13, -14, -15 and -24 decreased, t...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Lin TS,Chiou SH,Wang LS,Huang HH,Chiang SF,Shih AY,Chen YL,Chen CY,Hsu CP,Hsu NY,Chou MC,Kuo SJ,Chow KC

    更新日期:2004-10-01 00:00:00

  • Sanguinarine-induced apoptosis in lung adenocarcinoma cells is dependent on reactive oxygen species production and endoplasmic reticulum stress.

    abstract::Sanguinarine (SAN), an alkaloid isolated from plants of the Papaveraceae family, is a compound with multiple biological activities. In the present study, we explored the anticancer properties of SAN in lung cancer using the human lung adenocarcinoma cell line SPC-A1. Our results revealed that SAN inhibited SPC-A1 cell...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4054

    authors: Gu S,Yang XC,Xiang XY,Wu Y,Zhang Y,Yan XY,Xue YN,Sun LK,Shao GG

    更新日期:2015-08-01 00:00:00

  • In vivo real-time imaging of chemotherapy response on the liver metastatic tumor microenvironment using multiphoton microscopy.

    abstract::In vivo real-time visualization of chemotherapy response at the cellular level provides us with direct evidence of what happens on the tumor microenvironment of metastatic organs. We imaged the response of metastatic tumor cells and host stromal cells to chemotherapeutics on liver m...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1983

    authors: Tanaka K,Okigami M,Toiyama Y,Morimoto Y,Matsushita K,Kawamura M,Hashimoto K,Saigusa S,Okugawa Y,Inoue Y,Uchida K,Araki T,Mohri Y,Mizoguchi A,Kusunoki M

    更新日期:2012-11-01 00:00:00

  • Recombinant hirudin suppresses the viability, adhesion, migration and invasion of Hep-2 human laryngeal cancer cells.

    abstract::Recombinant hirudin (rH) is a highly potent and specific inhibitor of thrombin, and has been shown to inhibit the growth and metastasis of several types of cancers in experimental tumor models. The objective of this study was to evaluate the antitumor effects and explore the underlying mechanisms of rH in Hep-2 human ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.3717

    authors: Lu Q,Lv M,Xu E,Shao F,Feng Y,Yang J,Shi L

    更新日期:2015-03-01 00:00:00

  • Identification of intragenic methylation in the TUSC1 gene as a novel prognostic marker of hepatocellular carcinoma.

    abstract::Patients with hepatocellular carcinoma (HCC) have a poor prognosis, and novel molecular targets for treating recurrence and progression of the disease along with associated biomarkers are urgently required. In the present study, expression and the regulatory mechanism of TUSC1 (tumor suppressor candidate 1) were inves...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2939

    authors: Shimizu D,Kanda M,Nomoto S,Oya H,Takami H,Hibino S,Suenaga M,Inokawa Y,Hishida M,Takano N,Nishikawa Y,Yamada S,Fujii T,Nakayama G,Sugimoto H,Koike M,Fujiwara M,Kodera Y

    更新日期:2014-03-01 00:00:00

  • MicroRNA and target mRNA selection through invasion and cytotoxicity cell modeling and bioinformatics approaches in esophageal squamous cell carcinoma.

    abstract::This study analyzed microRNA (miRNA) and mRNA expression profiles and investigated the biological characteristics of ESCC by using invasion and cytotoxicity cell models. miRNA profiles were evaluated through miRNA microarray. Transwell chamber and nedaplatin (NDP) were used to construct invasion and cytotoxicity cell ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5776

    authors: Lu M,Song Y,Fu W,Liu Y,Huai S,Cui X,Pang L,Yang L,Wei Y

    更新日期:2017-08-01 00:00:00

  • Antitumor effect of COOH-terminal polypeptide of human TERT is associated with the declined expression of hTERT and NF-κB p65 in HeLa cells.

    abstract::Human telomerase reverse transcriptase (hTERT) plays an important role in the development of tumors and has been investigated as a potent target for anticancer therapy. In the present study, we constructed a recombinant adenovirus, Ad-EGFP-C197 which was capable of expressing COOH‑terminal polypeptide of hTERT (amino ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4298

    authors: Wu X,Chen J,Cao Y,Xie B,Li H,Zhou P,Qiu Y,Pang J

    更新日期:2015-12-01 00:00:00

  • Epigenetic modulation of AR gene expression in prostate cancer DU145 cells with the combination of sodium butyrate and 5'-Aza-2'-deoxycytidine.

    abstract::The androgen receptor (AR) plays an essential role in the development and progression of prostate cancer. Castration-resistant prostate cancer (CRPC) is a consequence of androgen deprivation therapy. Unchecked CRPC followed by metastasis is lethal. Some CRPCs show decreased AR gene expression due to epigenetic mechani...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5000

    authors: Fialova B,Luzna P,Gursky J,Langova K,Kolar Z,Trtkova KS

    更新日期:2016-10-01 00:00:00

  • Expression of MMP-2, -7, -9, MT1-MMP and TIMP-1 and -2 has no prognostic relevance in patients with advanced epithelial ovarian cancer.

    abstract::Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tumor invasion, but their prognostic significance is still under discussion. We set out to analyze the epithelial and stromal expression of MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1 and TIMP-2 in advanced epithelial ovarian cancers and to ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1608

    authors: Brun JL,Cortez A,Lesieur B,Uzan S,Rouzier R,Daraï E

    更新日期:2012-04-01 00:00:00

  • Unfavorable clinical implications for hypermethylation of RUNX3 in patients with salivary gland adenoid cystic carcinoma.

    abstract::To elucidate the potential etiological role of RUNX3 in the development of salivary gland adenoid cystic carcinoma (ACC), we analyzed the methylation status of RUNX3 in a series of 114 ACC tissues and 3 ACC cell lines. Results showed that the methylated rate of RUNX3 was 50.9 and 3.5% in the 114 ACC samples and the co...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1282

    authors: Ge MH,Chen C,Xu JJ,Ling ZQ

    更新日期:2011-08-01 00:00:00

  • Possible involvement of TGF‑β‑SMAD‑mediated epithelial‑mesenchymal transition in pro‑metastatic property of PAX6.

    abstract::Paired box 6 (PAX6) is a transcription factor that has oncogenic features. In breast cancer, PAX6 facilitates tumor progression; however, the underlying mechanism is largely unknown. The majority of breast cancer‑related mortalities are associated with metastasis of cancer cells. Therefore, the present study aimed to ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7644

    authors: Jin M,Gao D,Wang R,Sik A,Liu K

    更新日期:2020-08-01 00:00:00

  • MicroRNA‑577 inhibits the migration and invasion of hepatocellular carcinoma cells by targeting homeobox A1.

    abstract::Research has confirmed that abnormally expressed miRNAs are involved in the occurrence and development of hepatocellular carcinoma (HCC). In the present study, we confirmed that miR‑577 expression both in HCC tissues and cell lines was markedly downregulated. Clinically, downregulated expression of miR‑577 is notably ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6388

    authors: Han S,Liu Z,Wang Y,Wang L,Yao B,Guo C,Song T,Tu K,Liu Q

    更新日期:2018-06-01 00:00:00

  • Transcribed ultraconserved region Uc.63+ promotes resistance to cisplatin through regulation of androgen receptor signaling in bladder cancer.

    abstract::Cisplatin (CDDP)‑based combination chemotherapy is the standard for muscle‑invasive bladder cancer (MIBC). However, nearly all patients undergoing CDDP chemotherapy become refractory due to the development of CDDP resistance. Therefore, clarification of the mechanisms of CDDP resistance is urgently needed. The transcr...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7039

    authors: Sekino Y,Sakamoto N,Ishikawa A,Honma R,Shigematsu Y,Hayashi T,Sentani K,Oue N,Teishima J,Matsubara A,Yasui W

    更新日期:2019-05-01 00:00:00

  • Silencing of CKIP-1 promotes tumor proliferation and cell adhesion-mediated drug resistance via regulating AKT activity in non-Hodgkin's lymphoma.

    abstract::Casein kinase 2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is involved in regulating many processes such as cell proliferation, differentiation and apoptosis. CKIP-1 also plays an important role in many types of cancer, such as colon, breast cancer and human osteosarcoma. In the present study, we found that...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5233

    authors: Zhu X,Ouyang Y,Zhong F,Wang Q,Ding L,Zhang P,Chen L,Liu H,He S

    更新日期:2017-01-01 00:00:00

  • The novel bis-benzylisoquinoline PY35 reverses P-glycoprotein-mediated multidrug resistance.

    abstract::Multidrug resistance (MDR) to chemotherapeutic drugs is the main cause of chemotherapy failure in cancer treatment, and it generally results from expression of ATP-dependent efflux pump P-glycoprotein (P-gp). MDR reversal agents typically act by inhibiting the drug efflux activity of P-gp, thereby increasing intracell...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3326

    authors: Cao Z,Wright M,Cheng J,Huang X,Liu L,Wu L,Yang P

    更新日期:2014-09-01 00:00:00

  • Inhibition of cell growth and induction of apoptosis in human prostate cancer cell lines by 6-aminoquinolone WM13.

    abstract::Fluoroquinolones affect the proliferation and apoptotic cell death of several human malignancies. Therefore, we investigated whether new 6-aminoquinolone derivatives, initially synthesized as anti-HIV agents, could affect the proliferation and apoptotic cell death of human prostate cancer cell lines. PC3 and LNCaP cel...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Minelli A,Bellezza I,Siciliano E,Liguori L,Tabarrini O,Cecchetti V,Fravolini A

    更新日期:2005-06-01 00:00:00

  • Retinoic acid induces differentiation in neuroblastoma via ROR1 by modulating retinoic acid response elements.

    abstract::Neuroblastoma is the most common inheritable, solid neoplasm in children found under the age of 7 and accounts for approximately 7% of childhood cancers. A common treatment that has been prescribed for over a decade is retinoid therapy [using all‑trans retinoic acid (RA)]. Treatment with this differentiating agent has...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7681

    authors: Illendula A,Fultang N,Peethambaran B

    更新日期:2020-09-01 00:00:00

  • Daily or weekly dosing with EGFR inhibitors, gefitinib and lapatinib, and AKt inhibitor MK2206 in mammary cancer models.

    abstract::Daily vs. weekly dosing with EGFR inhibitors (gefitinib and lapatinib) and an AKT inhibitor (MK2206) were compared in two rodent breast cancer models. Female Sprague-Dawley rats were administered methylnitrosourea (MNU) at 50 days of age, and gefitinib (daily/weekly dosing at 10/70 mg/kg BW) or lapatinib (daily/weekly...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6313

    authors: Lubet RA,Steele VE,Juliana MM,Bode A,Moeinpour F,Grubbs CJ

    更新日期:2018-09-01 00:00:00

  • Decreased expression of long non-coding RNA GAS5 promotes cell proliferation, migration and invasion, and indicates a poor prognosis in ovarian cancer.

    abstract::Long non-coding RNA growth arrest-specific 5 (GAS5) was reported to be aberrantly expressed in various types of cancers. However, the role of GAS5 in the evolution and progression of ovarian cancer remains elusive. In the present study, we aimed to investigate the cellular function and clinical significance of GAS5 in...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5200

    authors: Li J,Huang H,Li Y,Li L,Hou W,You Z

    更新日期:2016-12-01 00:00:00

  • Photosensitizer effect of curcumin on UVB-irradiated HaCaT cells through activation of caspase pathways.

    abstract::Photodynamic therapy (PDT) using photosensitizer can induce diverse cellular responses, including apoptosis. Recently, it has been reported that PDT using methylaminolaevulinate may be effective in basal cell carcinoma. However, it is largely unknown whether PDT using a natural product such as curcumin can induce apop...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Park K,Lee JH

    更新日期:2007-03-01 00:00:00