A quadruple therapy synergistically blocks proliferation and promotes apoptosis of hepatoma cells.

Abstract:

:Effective therapy for advanced hepatocellular carcinoma (HCC) is lacking. Conventional chemotherapy was judged to be ineffective. We previously demonstrated that the histone deacetylase inhibitor Trichostatin A (TSA) blocks growth of HCC cells in vitro. The anti-tumoral effect of a combination of more than 2 classes of drugs remains unexplored. Four hepatoma cell lines were incubated with increasing concentrations of Tamoxifen (TAM), 9-cis retinoic acid (CRA), the methioninaminopeptidase inhibitor TNP-470 and TSA as single agents and in combination. Anti-proliferative and pro-apoptotic effects were assessed using BrdU-incorporation, FACS analysis and immunocytochemistry. Central pro- and anti-apoptotic proteins were measured by semi-quantitative Western blotting and substrate assays. All single substances inhibited proliferation and induced apoptosis in HCC cells only at high concentrations. The combination of TAM/CRA/TNP/TSA multiplied the anti-tumoral effects, reaching up to 93% inhibition of proliferation and 63% induction of apoptosis after 24 h in Hep1B cells. Pro-apoptotic factors bax and caspase 3 were highly increased with quadruple therapy, while anti-apoptotic bcl-2 decreased to undetectable levels. Fibroblasts remained largely unaffected. While the single substances were not effective on hepatoma cells in tolerable doses, their combination significantly increases anti-tumoral efficacy. Combination therapy with biomodulators is a promising treatment option for HCC.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Ganslmayer M,Ocker M,Zopf S,Leitner S,Hahn EG,Schuppan D,Herold C

keywords:

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

943-50

issue

5

eissn

1021-335X

issn

1791-2431

journal_volume

11

pub_type

杂志文章
  • Increased expression and activity of p75NTR are crucial events in azacitidine-induced cell death in prostate cancer.

    abstract::The high affinity nerve growth factor (NGF) NGF receptor, p75NTR, is a member of the tumor necrosis factor (TNF) receptor superfamily that shares a conserved intracellular death domain capable of inducing apoptosis and suppressing growth in prostate epithelial cells. Expression of this receptor is lost as prostate can...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4832

    authors: Gravina GL,Marampon F,Sanità P,Mancini A,Colapietro A,Scarsella L,Jitariuc A,Biordi L,Ficorella C,Festuccia C

    更新日期:2016-07-01 00:00:00

  • Regulation of BGC-823 cell sensitivity to adriamycin via miRNA-135a-5p.

    abstract::MicroRNAs (miRNAs) play an important role in the genesis and development of gastric cancer. In the present study, we determined whether miRNA-135a-5p expression was increased in gastric cancer compared with adjacent non-tumor tissues using 20 pairs of gastric cancer and para-carcinoma tissue samples which were assesse...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3546

    authors: Pan Y,Ren F,Zhang W,Liu G,Yang D,Hu J,Feng K,Feng Y

    更新日期:2014-12-01 00:00:00

  • Expression of immune checkpoint molecules of T cell immunoglobulin and mucin protein 3/galectin-9 for NK cell suppression in human gastrointestinal stromal tumors.

    abstract::Monoclonal antibody therapy for immune checkpoint blockade has achieved promising results for several types of malignant tumors. For the future treatment of gastrointestinal stromal tumors (GISTs) by immune checkpoint blockade, expression of immune checkpoint-related molecules that suppress antitumor immunity in GISTs...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4149

    authors: Komita H,Koido S,Hayashi K,Kan S,Ito M,Kamata Y,Suzuki M,Homma S

    更新日期:2015-10-01 00:00:00

  • miR-17-5p promotes the growth of osteosarcoma in a BRCC2-dependent mechanism.

    abstract::MicroRNA-17-5p has been proven upregulated in many human malignancies and correlated with tumor progression. However, its expression and clinical significance in osteosarcoma is still unclear. Thus, the aim of the present study was to explore the effects of miR-17-5p in osteosarcoma tumorigenesis and development. The ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4542

    authors: Wang W,Zhang L,Zheng K,Zhang X

    更新日期:2016-03-01 00:00:00

  • Induction of eEF2-specific antitumor CTL responses in vivo by vaccination with eEF2-derived 9mer-peptides.

    abstract::Eukaryotic elongation factor 2 (eEF2) is an essential factor for protein synthesis. Previous studies have shown that the eEF2 gene was overexpressed and plays an oncogenic role in various types of cancers and that eEF2 gene product elicited both humoral immune responses to produce eEF2-specific IgG autoantibody in can...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4589

    authors: Nakajima H,Murakami Y,Morii E,Akao T,Tatsumi N,Odajima S,Fukuda M,Machitani T,Iwai M,Kawata S,Hojo N,Oka Y,Sugiyama H,Oji Y

    更新日期:2016-04-01 00:00:00

  • β‑carotene reverses tobacco smoke‑induced gastric EMT via Notch pathway in vivo.

    abstract::Tobacco smoke is one of the serious risk factors of gastric cancer. Epithelial‑mesenchymal transition (EMT) has been shown to be associated with the initiation and carcinogenesis of gastric cancer. The role of Notch pathway in regulating tobacco smoke-induced EMT has not been investigated. β‑carotene, a carotenoid pre...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6246

    authors: Lu L,Chen J,Li M,Tang L,Wu R,Jin L,Liang Z

    更新日期:2018-04-01 00:00:00

  • SOCS4 expressed by recombinant HSV protects against cytokine storm in a mouse model.

    abstract::Oncolytic viruses are genetically engineered viruses designed for the treatment of solid tumors, and are often coupled with the antitumor immunity of the host. The challenge of using oncolytic herpes simplex virus (oHSV) as an efficacious oncolytic agent is the potential host tissue damage caused by the production of ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6935

    authors: Ren S,Chen X,Huang R,Zhou GG,Yuan Z

    更新日期:2019-03-01 00:00:00

  • Lactoferrin immunoexpression in endometrial carcinomas: relationships with sex steroid hormone receptors (ER and PR), proliferation indices (Ki-67 and AgNOR) and survival.

    abstract::We have investigated Lf immunoexpression as well as its biological meaning in 71 formalin-fixed, paraffin-embedded surgical samples of endometrial carcinomas (EC); 64 EC were endometrioid type, whereas 7 were non-endometrioid carcinomas. Immunohistochemistry was performed by primary antibodies against Lactoferrin (Lf)...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Giuffrè G,Arena F,Scarfì R,Simone A,Todaro P,Tuccari G

    更新日期:2006-08-01 00:00:00

  • 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 essent...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4850

    authors: Dai Y,Cui J,Gan P,Li W

    更新日期:2016-08-01 00:00:00

  • Nitidine chloride suppresses epithelial-to-mesenchymal transition in osteosarcoma cell migration and invasion through Akt/GSK-3β/Snail signaling pathway.

    abstract::Metastasis is the main cause of death in osteosarcoma. Targeting the process of metastasis is a main strategy for osteosarcoma therapy. As a traditional Chinese medicine, Zanthoxylum nitidum (Roxb) has been applied to treat various diseases, including cancer. However, no evidence has been shown on the anti-metastasis ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4846

    authors: Cheng Z,Guo Y,Yang Y,Kan J,Dai S,Helian M,Li B,Xu J,Liu C

    更新日期:2016-08-01 00:00:00

  • Ibuprofen enhances TRAIL-induced apoptosis through DR5 upregulation.

    abstract::Numerous human chemoprevention studies have demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) possess chemopreventive effects against a variety of malignant tumors. However, there have been many clinical studies on aspirin, but not ibuprofen, even though ibuprofen is one of the most clinically and safel...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2713

    authors: Todo M,Horinaka M,Tomosugi M,Tanaka R,Ikawa H,Sowa Y,Ishikawa H,Fujiwara H,Otsuji E,Sakai T

    更新日期:2013-11-01 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

  • Evaluation of ERalpha, PR and ERbeta isoforms in neoadjuvant treated breast cancer.

    abstract::The actual predictive value of oestrogen receptor (ER) beta for treatment decisions in breast cancer is still unclear. Retrospective studies using preoperative systemic therapy (PST) revealed that chemotherapy but also endocrine therapy can lead to alterations in expression levels of ERalpha and progesterone receptor ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Wurster M,Ruoff A,Meisner C,Seeger H,Vogel U,Juhasz-Böss I,Solomayer E,Wallwiener D,Fehm T,Neubauer H

    更新日期:2010-09-01 00:00:00

  • Pathomorphological study on small nodular lesions in hepatitis C virus-related cirrhosis.

    abstract::We examined pathomorphologically small nodular lesions in hepatitis C virus-related cirrhosis (type C cirrhosis). Small nodular lesions seen in the non-cancerous areas of 128 consecutively resected hepatocellular carcinomas (HCCs) associated with type C cirrhosis were selected for the study. From these, 18 large regen...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Miyaaki H,Fujimoto M,Kurogi M,Nakashima O,Eguchi K,Kojiro M

    更新日期:2005-12-01 00:00:00

  • Reduced expression and loss of heterozygosity of the SDHD gene in colorectal and gastric cancer.

    abstract::Mitochondrial DNA (mtDNA) mutations occur in a variety of human cancers, suggesting a possible role for mitochondrial respiratory functions in tumorigenesis. Recent studies have demonstrated that SDHD, a nuclear gene encoding one of the mitochondrial complex II subunits, acts as a tumor-suppressor for hereditary parag...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Habano W,Sugai T,Nakamura S,Uesugi N,Higuchi T,Terashima M,Horiuchi S

    更新日期:2003-09-01 00:00:00

  • The expression of hDlg as a biomarker of the outcome in malignant fibrous histiocytomas.

    abstract::The human homologue of Drosophila disc large tumor suppressor protein (hDlg) is one of the proteins known to act cooperatively in regulating cell polarity and proliferation, suggesting an important connection between epithelial organization and cellular growth control. An abnormal expression of hDlg has been reported ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000678

    authors: Niimi R,Matsumine A,Iino T,Murata T,Shintani K,Nakazora S,Nakamura T,Uehara Y,Kusuzaki K,Akiyama T,Uchida A

    更新日期:2010-03-01 00:00:00

  • Detection of activated K-ras in non-small cell lung cancer by membrane array: a comparison with direct sequencing.

    abstract::The ability to detect K-ras oncogene may provide additional information for the management of patients with non-small cell lung cancer (NSCLC). In the present study, we detected the K-ras oncogene in 76 patients with NSCLC by two methods: direct sequencing of K-ras in tumor tissues and membrane array detection of the ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Chong IW,Chang MY,Sheu CC,Wang CY,Hwang JJ,Huang MS,Lin SR

    更新日期:2007-07-01 00:00:00

  • In vitro and in vivo magnetic resonance imaging with chlorotoxin-conjugated superparamagnetic nanoprobes for targeting hepatocarcinoma.

    abstract::The present study aimed to assess the in vitro and in vivo magnetic resonance imaging (MRI) features of chlorotoxin (CTX)-conjugated superparamagnetic iron oxide (SPIO) nanoprobes. CTX-conjugated nanoprobes were composed of SPIO coated with polyethylene glycol (PEG) and conjugated with CTX. The nanoprobes were termed ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4629

    authors: Chen Z,Xiao EH,Kang Z,Zeng WB,Tan HL,Li HB,Bian DJ,Shang QL

    更新日期:2016-05-01 00:00:00

  • MicroRNA-152 inhibits tumor cell growth by directly targeting RTKN in hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is the most common form of adult liver cancer and accounts for approximately 90% of all cases of primary liver cancer annually. Rhotekin (RTKN), which functions as a cancer promoter, can be frequently detected in many human cancers, including gastric cancer, colorectal carcinoma and blad...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5290

    authors: Zhou J,Zhang Y,Qi Y,Yu D,Shao Q,Liang J

    更新日期:2017-02-01 00:00:00

  • Non‑coding RNAs that regulate the Wnt/β‑catenin signaling pathway in gastric cancer: Good cop, bad cop? (Review).

    abstract::Gastric cancer (GC) is one of the most common causes of cancer‑related mortality worldwide. Despite remarkable progress in the diagnosis and treatment of GC, a large number of cases are diagnosed as advanced GC, and treatment failure occurs. Emerging evidence has shown that non‑coding RNAs (ncRNAs), especially microRN...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7705

    authors: Shao Z,Gao D,Chen L,Ding W,Yu Q

    更新日期:2020-10-01 00:00:00

  • [Corrigendum] MicroRNA-375 inhibits glioma cell proliferation and migration by downregulating RWDD3 in vitro.

    abstract::The authors of the above article drew to our attention that they had identified three instances of data overlapping between data panels, suggesting that data purportedly showing results obtained under different experimental conditions had been derived from the same original source. Comparing between the two figures, t...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7738

    authors: Ji CX,Fan YH,Xu F,Lv SG,Ye MH,Wu MJ,Zh XG,Wu L

    更新日期:2020-11-01 00:00:00

  • High-risk human papillomavirus E6/E7 mRNA and L1 DNA as markers of residual/recurrent cervical intraepithelial neoplasia.

    abstract::The aim of this study was to assess the use of human papillomavirus (HPV) E6/E7 mRNA testing in the follow-up of women treated for cervical intraepithelial neoplasia (CIN) by conization and to compare the prognostic value of HPV E6/E7 mRNA to HPV L1 DNA and cytology. One hundred and...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1755

    authors: Persson M,Brismar Wendel S,Ljungblad L,Johansson B,Weiderpass E,Andersson S

    更新日期:2012-07-01 00:00:00

  • A combined strategy of conventional cytogenetics, fluorescent in situ hybridization and microsatellite polymerase chain reaction to analyze the deletion of chromosome 6 in laryngeal squamous cell carcinoma.

    abstract::Laryngeal squamous cell carcinoma (LSCC) is a common cancer of the upper respiratory tract. The cytogenetic and molecular events involved in the pathogenesis of LSCC are not well understood. In this study, a combined strategy of conventional cytogenetics, fluorescent in situ hybridization (FISH) and microsatellite pol...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Kang N,Li F,Fu W,Zhang J,Sun K

    更新日期:2007-12-01 00:00:00

  • Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene.

    abstract::The objective of the present study was to explore the in vitro and in vivo anticancer effects of Platycodin D (PD), derived from Platycodin grandiflorum, on highly metastatic MDA-MB-231 breast cancer cells. Using the MTT assay, we found that PD inhibited MDA-MB-231 cell growth in a concentration-dependent manner, with...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4935

    authors: Kong Y,Lu ZL,Wang JJ,Zhou R,Guo J,Liu J,Sun HL,Wang H,Song W,Yang J,Xu HX

    更新日期:2016-09-01 00:00:00

  • Peptides and small molecules blocking the CXCR4/CXCL12 axis overcome bone marrow‑induced chemoresistance in acute leukemias.

    abstract::Notable advances in treatment have been made and increases in the cure rates of pediatric leukemia have been achieved. However, the majority of children with relapsed disease are not expected to survive, with chemotherapy resistance acting as the principal cause of treatment failure. Interaction between leukemic cells...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6808

    authors: Pillozzi S,Bernini A,Spiga O,Lelli B,Petroni G,Bracci L,Niccolai N,Arcangeli A

    更新日期:2019-01-01 00:00:00

  • Tanshinone IIA can inhibit MiaPaCa‑2 human pancreatic cancer cells by dual blockade of the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways.

    abstract::Tanshinone IIA (Tan‑IIA; C19H18O3) is derived from Danshen (the roots of Salvia miltiorrhiza), and has been reported to possess anti‑inflammatory and antioxidant activities. Tan‑IIA can inhibit BxPC‑3 human pancreatic cancer cells in vitro through inducing endoplasmic reticulum stress and apoptosis via mitochondrial p...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6670

    authors: Su CC

    更新日期:2018-11-01 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

  • Frizzled2 mediates the migration and invasion of human oral squamous cell carcinoma cells through the regulation of the signal transducer and activator of transcription-3 signaling pathway.

    abstract::Frizzled2 (Fzd2) is a receptor for wingless-type MMTV integration site family members (Wnts), the aberrant overexpression of which has been noted to contribute to cancer metastasis. The present study was performed to characterize the role of Fzd2 in the migration and invasion of oral squamous cell carcinomas (OSCC) in...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4285

    authors: Zhang E,Li Z,Xu Z,Duan W,Sun C,Lu L

    更新日期:2015-12-01 00:00:00

  • Chemokines mediate mesenchymal stem cell migration toward gliomas in vitro.

    abstract::Previous studies have demonstrated the tremendous tropism of mesenchymal stem cells (MSCs) for malignant gliomas, making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells. However, the mechanisms underlying the tropism of MSCs for gliomas remain poorly defined. It has been ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000796

    authors: Xu F,Shi J,Yu B,Ni W,Wu X,Gu Z

    更新日期:2010-06-01 00:00:00

  • Radioiodine-labeled anti-epidermal growth factor receptor binding bovine serum albumin-polycaprolactone for targeting imaging of glioblastoma.

    abstract::The aim of this study was to look for a new medicine in diagnosing and treating of glioblastoma. Radioiodine-labeled anti-epidermal growth factor receptor (EGFR) binding nanoparticles were constructed. In vitro cell-binding assays were confirmed by confocal microscopy and flow cytometry. Cell cytotoxicity assays were ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5937

    authors: Li C,Tan J,Chang J,Li W,Liu Z,Li N,Ji Y

    更新日期:2017-11-01 00:00:00