DPP3 Expression Promotes Cell Proliferation and Migration in Vitro and Tumor Growth in Vivo That Associates with Poor Prognosis of Esophageal Carcinoma

Abstract Background: Dipeptidyl peptidase III (DPP3) is a zinc-dependent metallopeptidase and elevated in a variety of malignant tumors, but the underlying mechanism is not well understood so far. Here we investigated the association of esophageal carcinogenesis with the regulation of DPP3 expression by tissue-based quantitative analysis and the depletion of DPP3 expression in esophageal cancer cells and xenograft model. Methods: The expression level of DPP3 in esophageal cancer tissues and adjacent normal tissues was detected in 93 cases of tissue biopsies collected from patients diagnosed with esophageal carcinoma by immunohistochemistry. The effect of DPP3 expression on cell proliferation, migration or apoptosis was determined in DPP3-depleted esophageal cancer cells created by infection with the lentivirus containing the shRNA specific to human DPP3 mRNA sequence followed by cytometric detection using celigo cell count assay, flow cytometry, wound-healing assay and trans-well assay as well as chip screening with a Human Apoptosis Antibody Array kit, which enables the quantitative detection of 43 apoptosis-related genes. A xenograft model was applied to the detection of tumor growth and invasion of DPP3-depleted cancer cells in nude mice.Results: DPP3 expression was elevated in esophageal cancer tissues compared with adjacent non-tumor tissues (normal controls) with statistical significance (P<0.05), and associated with poor prognosis of esophageal carcinoma. The DPP3-depletion resulted in a reduced cell proliferation and migration and enhanced cell-cycle arrest and apoptosis of esophageal cancer cells, and lead to the inhibition of tumor growth and invasion in xenograft model. In addition, DPP3-depletion was associated with the upregulation of pro-apoptotic proteins and the downregulation of anti-apoptotic proteins.Conclusions: These findings suggest that DPP3 may promote cell proliferation, migration and survival of esophageal cancer cells in vitro, and tumor growth and invasion of esophageal carcinoma in vivo and this might serve as a molecular target for tumor therapy.

Download Full-text

Ribophorin II promotes cell proliferation, migration, and invasion in esophageal cancer cells in vitro and in vivo

Bioscience Reports ◽

10.1042/bsr20182448 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 3

Author(s):

Yongshun Li ◽

Changrong Huang ◽

Qizhou Bai ◽

Jun Yu

Keyword(s):

Cell Proliferation ◽

Esophageal Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Migration And Invasion ◽

Cancer Tissues ◽

Esophageal Cancer Cells ◽

E Cadherin

AbstractEsophageal cancer is a common digestive tract cancer, which is a serious threat to human health. Ribophorin II (RPN2) is a part of an N-oligosaccharyltransferase complex, which is excessively expressed in many kinds of cancers. In the present study, we explore the biological role of RNP2 in esophageal cancer. First, we found that the expression of RPN2 was higher in esophageal cancer tissues than in adjacent non-tumor tissues, and negatively correlated with E-cadherin expression. RPN2 expression levels in esophageal cancer tissues were positively associated with differentiation and tumor node metastasis (TNM) stage. Furthermore, the expression of RPN2 was increased significantly in esophageal cancer cell lines compared with normal cells. The effect of RPN2 down-regulation on cell proliferation, cell migration, and cell invasion was examined by cell counting kit-8 (CCK8), wound healing assay, and Transwell assay, respectively. Silencing RPN2 effectively inhibited cell proliferation of esophageal cancer cells in vitro and in vivo. Cell migration and invasion were also weakened dramatically by siRPN2 treatment of esophageal cancer cells. In addition, protein expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP-2), and E-cadherin in esophageal cancer cells was determined by Western blot analysis. PCNA, MMP-2, E-cadherin, Snail and phosphorylation-Smad2/3 expression was also regulated notably by siRPN2 treatment. These findings indicate that RPN2 exhibits oncogenetic capabilities in esophageal cancer, which could provide novel insights into esophageal cancer prevention and treatment.

Download Full-text

Hesperetin inhibits Eca-109 cell proliferation and invasion by suppressing the PI3K/AKT signaling pathway and synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal cancer in vitro and in vivo

RSC Advances ◽

10.1039/c8ra00956b ◽

2018 ◽

Vol 8 (43) ◽

pp. 24434-24443 ◽

Cited By ~ 2

Author(s):

Dandan Wu ◽

Jiao Li ◽

Xue Hu ◽

Jingjing Ma ◽

Weiguo Dong

Keyword(s):

Cell Proliferation ◽

Esophageal Cancer ◽

Cancer Cells ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Anti Cancer ◽

Esophageal Cancer Cells ◽

Proliferation And Invasion

Effects of hesperetin on the proliferation and invasion of esophageal cancer cells and its synergistic anti-cancer effect with 5-FU.

Download Full-text

Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo

Journal of Cancer ◽

10.7150/jca.21224 ◽

2018 ◽

Vol 9 (1) ◽

pp. 32-40 ◽

Cited By ~ 11

Author(s):

Jian-Cai Tang ◽

Jia Zhao ◽

Feng Long ◽

Jian-ye Chen ◽

Bo Mu ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Esophageal Cancer Cells

Download Full-text

Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro

Cancer Cell International ◽

10.1186/s12935-019-1061-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Chengjuan Zhang ◽

Junxia Zhang ◽

Qiong Wu ◽

Benling Xu ◽

Guoguo Jin ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Cell Apoptosis ◽

Biological Effects ◽

Migration And Invasion ◽

Global Changes ◽

Fcm Analysis ◽

Esophageal Cancer Cells

Abstract Background As a novel type of isothiocyanate derived from radish seeds from cruciferous vegetables, sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) has various important biological effects, such as anti-oxidative and anti-bacterial effects. Recently, sulforaphene has attracted increasing attention for its anti-tumor effects and its ability to suppress the development of multiple tumors through different regulatory mechanisms. However, it has not yet been widely investigated for the treatment of esophageal cancer. Methods We observed an increased apoptosis in esophageal cancer cells on sulforaphene treatment through flow cytometry (FCM) analysis and transmission electron microscopy (TEM). Through mass spectrometry (MS) analysis, we further detected global changes in the proteomes and phosphoproteomes of esophageal cancer cells on sulforaphene treatment. The molecular mechanism of sulforaphene was verified by western blot,the effect and mechanism of SFE on esophageal cancer was further verified by patient-derived xenograft mouse model. Results We identified multiple cellular processes that were changed after sulforaphene treatment by proteomics. We found that sulforaphene could repress the phosphorylation of CREB through MSK2, leading to suppression of Bcl-2 and further promoted cell apoptosis. Additionally, we confirmed that sulforaphene induces tumor cell apoptosis in mice. Interestingly, we also observed the obvious inhibition of cell migration and invasion caused by sulforaphene treatment by inhibiting the expression of cadherin, indicating the complex effects of sulforaphene on the development of esophageal cancer. Conclusions Our data demonstrated that sulforaphene induced cell apoptosis and inhibits the invasion of esophageal cancer through a mechanism involving the inhibition of the MSK2–CREB–Bcl2 and cadherin pathway. Sulforaphene could therefore serve as a promising anti-tumor drug for the treatment of esophageal cancer.

Download Full-text

The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo

Oncology Reports ◽

10.3892/or.17.4.887 ◽

2007 ◽

Cited By ~ 2

Author(s):

E. Ako ◽

Y. Yamashita ◽

M. Ohira ◽

M. Yamazaki ◽

T. Hori ◽

...

Keyword(s):

Esophageal Cancer ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Cancer Cells ◽

Kinase Inhibitor ◽

Human Esophageal Cancer ◽

Esophageal Cancer Cells

Download Full-text

The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation of the noncanonical Wnt signaling pathway

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90455.2008 ◽

2008 ◽

Vol 295 (6) ◽

pp. G1150-G1158 ◽

Cited By ~ 45

Author(s):

Sharon DeMorrow ◽

Heather Francis ◽

Eugenio Gaudio ◽

Julie Venter ◽

Antonio Franchitto ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Growth ◽

Wnt Signaling ◽

Signaling Pathway ◽

Calcium Release ◽

Wnt Signaling Pathway ◽

Xenograft Model ◽

Orphan Receptor

Cholangiocarcinomas are cancers that have poor prognosis and limited treatment options. The noncanonical Wnt pathway is mediated predominantly by Wnt 5a, which activates a Ca2+-dependent pathway involving protein kinase C, or a Ca2+-independent pathway involving the orphan receptor Ror2 and subsequent activation of Jun NH2-terminal kinase (JNK). This pathway is associated with growth-suppressing effects in numerous cell types. We have shown that anandamide decreases cholangiocarcinoma growth in vitro. Therefore, we determined the effects of anandamide on cholangiocarcinoma tumor growth in vivo using a xenograft model and evaluated the effects of anandamide on the noncanonical Wnt signaling pathways. Chronic administration of anandamide decreased tumor growth and was associated with increased Wnt 5a expression in vitro and in vivo. Treatment of cholangiocarcinoma cells with recombinant Wnt 5a decreased cell proliferation in vitro. Neither anandamide nor Wnt 5a affected intracellular calcium release, but both increased the JNK phosphorylation. Stable knockdown of Wnt 5a or Ror2 expression in cholangiocarcinoma cells abolished the effects of anandamide on cell proliferation and JNK activation. Modulation of the endocannabinoid system may be important in cholangiocarcinoma treatment. The antiproliferative actions of the noncanonical Wnt signaling pathway warrants further investigation to dissect the mechanism by which this may occur.

Download Full-text

Effects and Mechanisms of Metformin on the Proliferation of Esophageal Cancer Cells In Vitro and In Vivo

Cancer Research and Treatment ◽

10.4143/crt.2015.485 ◽

2017 ◽

Vol 49 (3) ◽

pp. 778-789 ◽

Cited By ~ 11

Author(s):

Jian-Cai Tang ◽

Rui An ◽

Yi-Qing Jiang ◽

Jian Yang

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Esophageal Cancer Cells

Download Full-text

Effect of doxycycline on proliferation, MMP production, and adhesion in LAM-related cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00437.2009 ◽

2010 ◽

Vol 299 (3) ◽

pp. L393-L400 ◽

Cited By ~ 26

Author(s):

William Y. C. Chang ◽

Debbie Clements ◽

Simon R. Johnson

Keyword(s):

Cell Proliferation ◽

Cell Adhesion ◽

Tumor Growth ◽

Xenograft Model ◽

Cyst Formation ◽

Randomized Controlled Clinical Trials ◽

Diphenyltetrazolium Bromide ◽

Mtt Reduction

Matrix metalloproteinases (MMPs) have been implicated in lung cyst formation in lymphangioleiomyomatosis (LAM). As doxycycline inhibits MMP activity in vivo, some patients take doxycycline, as one report has suggested a possible benefit in LAM. However, there have been no randomized controlled clinical trials of doxycycline for LAM, and any mechanism of action is unclear. Here, we examine previously proposed mechanisms of actions. Cell proliferation and adhesion were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and Cytomatrix cell adhesion kits. Apoptosis was examined by TdT-mediated dUTP nick end labeling (TUNEL) assay. MMP-2 expression was examined by quantitative real-time PCR and zymography in doxycycline-treated ELT3 cells and tumor growth using angiomyolipoma-derived tumor xenografts in nude mice. In ELT3 cells, ≥25 μg/ml doxycycline decreased proliferation, increased apoptosis, and caused a change in cell morphology associated with redistribution of actin stress filaments. Reduction in proliferation was also seen in human angiomyolipoma-derived cells. Cell adhesion to ECM proteins was decreased by doxycycline at 50 μg/ml and prevented detachment of already adherent cells. There was no effect of doxycycline on MMP-2 expression or activity in vitro. In the xenograft model, doxycycline (30 mg·kg−1·day−1) had no effect on tumor growth, final tumor weight, or tumor lysate MMP levels. Doxycycline at doses ≥ 25 μg/ml inhibited cell proliferation and adhesion, possibly by a toxic effect. Doxycycline had no effect on MMP-2 expression or activity or tumor growth in the xenograft model. Any possible in vivo effect is unlikely to be mediated by MMP-2 or reduced cell proliferation.

Download Full-text

Anticancer Effects of Dihydroartemisinin on Human Esophageal Cancer Cells In Vivo

Analytical Cellular Pathology ◽

10.1155/2018/8759745 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Cailing Jiang ◽

Shumin Li ◽

Yanjing Li ◽

Yuxian Bai

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Dependent Manner ◽

Esophageal Cancer Cell ◽

Human Esophageal Cancer ◽

Semisynthetic Derivative ◽

Esophageal Cancer Cells ◽

Dose Dependent

Despite recent advances in chemotherapy and surgical resection, the 5-year survival rate of esophageal cancer still remains at the low level. Therefore, it is very important to discover a new agent to improve the life expectancy of patients with esophageal cancer. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently exhibited promising anticancer activity against various cancer cells. But so far, the specific mechanism remains unclear. We have previously demonstrated that DHA reduced viability of esophageal cancer cells in a dose-dependent manner in vitro and induced cell cycle arrest and apoptosis. Here, we extended our study to further observe the efficacy of DHA on esophageal cancer cells in vivo. In the present study, for the first time, we found that DHA significantly inhibits cell proliferation in xenografted tumor compared with the control. The mechanism was that DHA induced cell apoptosis in both human esophageal cancer cell lines Eca109 and Ec9706 in vivo in a dose-dependent manner. The results suggested that DHA was a promising agent against esophageal cancer in the clinical treatment.

Download Full-text