Abstract:
:The synergistic effect of combined drug therapy provides an enhanced treatment for advanced liver cancer. We aimed to investigate the underlying mechanism of cetuximab sensitization by rapamycin in hepatoma cells. Four hepatoma cell lines, HepG2, HuH7, SNU-387, and SNU-449, were treated with cetuximab or cetuximab plus rapamycin and growth inhibition was evaluated by measuring relative cell viability and cell proliferation. The cell phenotype was determined for each hepatoma cell line by western blot analysis of E-cadherin and vimentin expression and mTOR activation status. To identify the role of mTOR signaling in cetuximab sensitization, we used deferoxamine-mediated hypoxia to induce epithelial-mesenchymal transition (EMT) in HuH7 and HepG2 cells and measured mTOR activity after rapamycin treatment. Rapamycin significantly increased cetuximab cytotoxicity in hepatoma cell lines with differential sensitivities. Phenotypic differences among hepatoma cell lines, specifically epithelial (HuH7 and HepG2) and mesenchymal (SNU-387 and SNU-449), correlated with the efficacy of rapamycin cotreatment, although rapamycin treatment did not affect cell phenotype. We further showed that rapamycin inhibits mTOR in mesenchymal SNU-387 and SNU-449 cells. In addition, the induction of EMT in HuH7 and HepG2 cells significantly decreased cetuximab cytotoxicity; however, rapamycin treatment significantly restored cetuximab sensitivity and decreased mTOR signaling in these cells. In conclusion, we identified significant differences in rapamycin-induced cetuximab sensitization between epithelial and mesenchymal hepatoma cells. We therefore report that rapamycin cotreatment enhances cetuximab cytotoxicity by inhibiting mTOR signaling in mesenchymal cells.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Chen W,Hu QD,Xia XF,Liang C,Liu H,Zhang Q,Ma T,Liang F,Liang TBdoi
10.4161/cbt.29113subject
Has Abstractpub_date
2014-08-01 00:00:00pages
992-9issue
8eissn
1538-4047issn
1555-8576pii
29113journal_volume
15pub_type
杂志文章abstract::SUMO (small ubiquitin-related modifier) represents a class of ubiquitin-like proteins that is conjugated, like ubiquitin, by a set of enzymes to cellular regulatory proteins, including oncogenes and tumor suppressor genes, that play key roles in the control of cell growth, differentiation and apoptosis. SUMO conjugati...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.74
更新日期:2002-05-01 00:00:00
abstract::Expression of the heparanase gene is associated with invasive, angiogenic and metastatic potential of diverse malignant tumors and cell lines. Here we used RNA interference strategies to evaluate the role of human heparanase in breast malignancy and to explore the therapeutic potential of its specific targeting. The s...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.4.3888
更新日期:2007-04-01 00:00:00
abstract::With the increasing interest in development of cytostatic anticancer drugs, the randomized discontinuation trial (RDT) design has been proved to be useful in the evaluation of their clinical activity. In the June 1, 2006 issue of the Journal of Clinical Oncology, a study by Ratain et al. uses RDT in a phase-II placebo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,随机对照试验
doi:10.4161/cbt.5.10.3290
更新日期:2006-10-01 00:00:00
abstract::Hes1 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability. Recent studies have shown that Hes1 functions in the maintenance of cancer stem cells (CSCs)...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.1080/15384047.2015.1016662
更新日期:2015-01-01 00:00:00
abstract::The molecular regulation of growth and progression of hormone refractory breast and prostate cancers remains challenging. The Division of Cancer Biology, NCI organized a small "think tank" style workshop and invited scientists in relevant areas to assess the state of science on the biology of hormone refractory tumors...
journal_title:Cancer biology & therapy
pub_type:
doi:10.4161/cbt.8.21.9918
更新日期:2009-11-01 00:00:00
abstract::CP-31398, a styrylquinazoline, emerged from a screen for therapeutic agents that restore a wild-type DNA-binding conformation of mutant p53 to suppress tumors in-vivo (Science 286, 2507, 1999). We investigated the growth inhibitory mechanism of CP-31398 using nine human cancer cell lines containing wild-type, mutant o...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.1.1.41
更新日期:2002-01-01 00:00:00
abstract::Li-Fraumeni syndrome (LFS) is primarily characterized by development of tumors exhibiting germ-line mutations in the p53 gene. Cell lines developed from patients of a LFS family have decreased p53 activity as evidenced by the absence of apoptosis upon etoposide treatment. To test our hypothesis that changes in gene ex...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.22621
更新日期:2013-01-01 00:00:00
abstract::Oncolytic viruses have recently received widespread attention for their potential in innovative cancer therapy. Many telomerase promoter-regulated oncolytic adenoviral vectors retain E1A and E1B. However, the functions of E1A and E1B proteins in the oncolytic role of replication-competent adenovirus (RCAd) and RCAd en...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.29842
更新日期:2014-10-01 00:00:00
abstract::Nucleophosmin (NPM)/B23, a multifunctional nucleolar protein, is overexpressed in actively proliferating cells and cancer cells. B23 is a tumor marker and exerts its oncogenic effect through binding and suppressing numerous tumor suppressors. NPM-ALK, an aberrant fusion protein produced from t(2;5) translocation in an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.4.9.2072
更新日期:2005-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.53
更新日期:2002-03-01 00:00:00
abstract:AIMS:Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity resulting in severe morbidity and mortality. To date only few proteins have been suggested as potential biomarkers or targets for this type of cancer. Cancerous inhibitor of PP2A (CIP2A) is a protein expressed in epithelial tis...
journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.10.7.12895
更新日期:2010-10-01 00:00:00
abstract::We investigated the expression of annexin-1 (ANXA1) in thyroid carcinoma cell lines and in thyroid cancers with a different degree of differentiation. The highest level of ANXA1 expression examined by Western blotting was detected in the papillary carcinoma cells (NPA) and in the follicular cells (WRO). On the other h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.6.2700
更新日期:2006-06-01 00:00:00
abstract::Every year, 12,000 people in the U.S. die from renal cell carcinoma. Current therapies include partial or complete nephrectomy or treatments such as administration of IFN-alpha and/or interleukins that are moderately effective, at best. Moreover, the current therapies are invasive and inefficient and new therapies are...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.10.2022
更新日期:2005-10-01 00:00:00
abstract::Insulin-like growth factor binding protein-7 (IGFBP7) is a gene identified as being low expressed in colorectal adenocarcinoma (CRC) cell lines. In the current study, we investigated the function of IGFBP7 in CRC by transfection studies. We found that IGFBP7 could inhibit cell growth, decrease soft agar colony formati...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.3.3702
更新日期:2007-03-01 00:00:00
abstract::Objective: To investigate the clinicopathologic features and immunophenotype of invasive-stratified mucin-producing carcinoma (ISMC). Methods: We retrospectively analyzed three patients who underwent surgery for pathologically confirmed ISMC from January 2017 to December 2017 in Anyang Tumor Hospital. The pathological...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2019.1647054
更新日期:2019-01-01 00:00:00
abstract::The pathogenesis of sporadic colorectal cancer involves distinct pathways, with characteristic genomic alterations. The first pathway, chromosome instability (CIN), is driven by APC mutations and is typified by Kras mutations, p53 mutation/loss of heterozygosity, and deletions at chromosome 18q. The second pathway is ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.22336
更新日期:2012-12-01 00:00:00
abstract::Current knowledge of changes in the mammary epithelium relevant to breast carcinogenesis is limited to when histological changes are already present because of a lack of biomarkers needed to identify where such molecular changes might be ongoing at earlier during the of decades-long latent stages of breast carcinogene...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.13.2.18873
更新日期:2012-01-15 00:00:00
abstract::GRP78, also referred to as BiP, is an essential molecular chaperone and a master regulator of the unfolded protein response. Traditionally, GRP78 is regarded as localized in the lumen of the endoplasmic reticulum (ER). However, recent findings revealed that a subfraction of GRP78 can localize to the surface of specifi...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.22.10140
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND INFORMATION:Previous studies have revealed that leptin may be involved in epithelial-mesenchymal transition (EMT), a crucial initiator of cancer progression to facilitate metastatic cascade, increase tumor recurrence, and ultimately cause poor prognosis. However, the underlying mechanism remains unclear. The...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1056409
更新日期:2015-01-01 00:00:00
abstract::Arsenic trioxide (As2O3) induces apoptosis in certain types of cancer cells. But the detailed mechanisms of As2O3 efficacy are not completely known. Here we demonstrate that As2O3 has a therapeutic effect on cervical cancer in vitro and in vivo. We investigated the As2O3-induced apoptosis in various cervical cancer ce...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.4.3887
更新日期:2007-04-01 00:00:00
abstract:EXPERIMENTAL DESIGN:To investigate the antitumor effect of sunitinib and FAK/Pyk2 tyrosine kinase inhibitor (PF-562,271)combination therapy in vivo, utilizing human hepatocellular carcinoma (HCC) cells Huh7.5. Nude rats were inoculated subcutaneously with Huh7.5 hepatoma cells. Dosing for Phase 1 was initiated on day 5...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.9.8246
更新日期:2009-05-01 00:00:00
abstract::Silibinin, derived from milk thistle extract, has been shown to inhibit growth factor receptor-mediated mitogenic and cell survival signaling, and to alter cell cycle regulators. Alteration in pathways regulating cell growth likely account for silibinin's inhibition of tumor growth. Since the epidermal growth factor r...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.2.5.452
更新日期:2003-09-01 00:00:00
abstract::Cell adhesion molecules (CAMs) are glycoproteins expressed on the surface of cell membranes. In normal cells, CAMs participate in a variety of biological processes including cell proliferation, migration and differentiation. In tumor cells, CAMs have been reported to function as oncogenes or tumor suppressors, in sign...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.8.4.7446
更新日期:2009-02-01 00:00:00
abstract:INTRODUCTION:Germ-line mutations of the APC gene are associated with familial adenomatous polyposis, and somatic mutations occur frequently in sporadic colorectal cancer. However, to abrogate APC function, both alleles must be inactivated. Recently, it has been demonstrated that epigenetic modification of the APC promo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.10.1113
更新日期:2004-10-01 00:00:00
abstract::While several hypotheses have been put forward to explain how prostate tumors become resistant to androgen deprivation therapy, the mechanism by which prostate tumors have increased androgen concentrations as compared to the serum has been poorly explored. Using a stromal/epithelial cell co-culture model, Mizokami et ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.3.11143
更新日期:2010-02-01 00:00:00
abstract::In a recent issue of Cancer Biology & Therapy, Vitale et al. introduced the paper of Franco et al. reporting the expression of GPER (a seven-transmembrane-spanning receptor also known as GPR30) on testicular germ cell tumors (TGCTs). The paper commented on the possible pathophysiological role of this G-protein-coupled...
journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.12.1.15726
更新日期:2011-07-01 00:00:00
abstract::The molecular phenotype of tumor vasculature is different from normal vasculature, offering new opportunities for diagnosis and therapy of cancer, but the identification of tumor-restricted targets remains a challenge. We investigated 13 tumor vascular markers (TVMs) from 50 candidates identified through expression pr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.3.16260
更新日期:2011-08-01 00:00:00
abstract::MicroRNAs (miRNAs), an important class of small regulatory molecules for gene expression, are transcribed by RNA polymerase II. But little is known about the mechanisms that control miRNA expression. Comparing miRNA expression profiles between colon cancer cell line HCT 116 and its derivative, DNA methyltransferase 1 ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.8.4486
更新日期:2007-08-01 00:00:00
abstract::Activation of MAP kinases is involved in various cellular processes, including immunoregulation, inflammation, cell growth, cell differentiation, and cell death. To investigate the role of p38 MAP kinase activation in the signaling pathway of TRAIL-mediated apoptosis, we compared TRAIL-mediated MAP kinase activation i...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.3.696
更新日期:2004-03-01 00:00:00
abstract::The discovery of microRNAs (miRNAs) has opened a new avenue for both diagnosis and treatment of cancers. Accumulating experimental evidences indicate that miRNAs are aberrantly expressed in different tumor types and have a critical role in tumorigenesis. However, the miRNA expression profile in neuroblastoma (NB), one...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.6.10894
更新日期:2010-03-15 00:00:00