Suppression of C6 Gliomas via Application of Rat Hyperplasia Gene

2014 ◽  
Vol 29 (4) ◽  
pp. 411-422 ◽  
Author(s):  
Peng Gao ◽  
Zhanwei Wang ◽  
Bin Zhang ◽  
Yourui Zou ◽  
Hui Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Recombinant Adenovirus ◽  
Glioma Cells ◽  
In Vivo Studies ◽  
Nuclear Antigen ◽  
Sprague Dawley ◽  
Rat Glioma ◽  
Suppression Mechanism

Background Among all neurological tumors, tumor incidence of the neuroepithelial tissue is the highest, where 50% are gliomas. Treatment for gliomas has traditionally included surgery and adjuvant therapy. With advancements in medicine, gene therapy has entered the clinical setting, in which control of tumor growth, tumor volume and decrease of supply of blood to the tumor have been observed. Rat hyperplasia suppressor gene (rHSG) has been proven to inhibit the injury-mediated proliferation of vascular smooth muscle cells. Methods A recombinant adenovirus, Adv-rHSG-GFP, was constructed and characterized by in vitro and in vivo studies. The function of rHSG on cell proliferation was determined in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) exclusion assay and plate clone formation, while a C6/Sprague Dawley rat glioma model was established to observe the effect of rHSG in vivo. Results Overexpression of rHSG displayed a strong effect on suppressing C6 cells proliferation in vitro and growth of glioma in vivo, which suggests the use of rHSG as a possible treatment strategy for glioma. p21Cip1, p27Kip1 and proliferating cell nuclear antigen were found to be involved in the tumor suppression mechanism of rHSG. Conclusions rHSG can markedly inhibit of the growth of rat glioma cells. The suppression mechanism of rHSG may be related to cell cycle regulation, which shows that rHSG is a potential therapeutic target of glioma tumor. This preclinical study supports a further in-depth study on the effect of rHSG on cell proliferation, migration and change in the extracellular matrix component of glioma cells.

scholarly journals Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2223
Author(s):  
Manon Dominique ◽  
Nicolas Lucas ◽  
Romain Legrand ◽  
Illona-Marie Bouleté ◽  
Christine Bôle-Feysot ◽  
...  
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Molecular Mimicry ◽  
Potential Effect ◽  
In Vivo Studies ◽  
Sprague Dawley ◽  
E Coli ◽  
In Vivo Effects

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague–Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.

scholarly journals Tip60 Suppresses Cholangiocarcinoma Proliferation and Metastasis via PI3k-AKT

2018 ◽  
Vol 50 (2) ◽  
pp. 612-628 ◽  
Author(s):  
Yaodong Zhang ◽  
Guwei Ji ◽  
Sheng Han ◽  
Zicheng Shao ◽  
Zefa Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Progression ◽  
Venous Invasion ◽  
In Vivo Studies ◽  
Akt Pathway ◽  
Rank Test ◽  
Aberrant Expression ◽  
Proliferation And Metastasis

Background/Aims: Aberrant expression of Tip60 is associated with progression in many cancers. However, the role of Tip60 in cancer progression remains contradictory. The aim of this study was to investigate the clinical significance, biological functions and underlying mechanisms of Tip60 deregulation in cholangiocarcinoma (CCA) for the first time. Methods: Quantitative real-time PCR (QRT-PCR), western blotting and immunohistochemistry staining (IHC) were carried out to measure Tip60 expression in CCA tissues and cell lines. Kaplan–Meier analysis and the log-rank test were used for survival analysis. In vitro, cell proliferation was evaluated by flow cytometry and CCK-8, colony formation, and EDU assays. Migration/ invasion was evaluated by trans-well assays. Phosphokinase array was used to confirm the dominant signal regulated by Tip60. Tumor growth and metastasis were demonstrated in vivo using a mouse model. Results: Tip60 was notably downregulated in CCA tissues, which was associated with greater tumor size, venous invasion, and TNM stage. Down-regulation of Tip60 was associated with tumor progression and poorer survival in CCA patients. In vitro and in vivo studies demonstrated that Tip60 suppressed growth and metastasis throughout the progression of CCA. We further identified the PI3K/AKT pathway as a dominant signal of Tip60 and suggested that Tip60 regulated CCA cell proliferation and metastasis via PT3K-AKT pathway. Pearson analysis revealed that PTEN was positively correlated with the Tip60 level in CCA tissues. Conclusion: Tip60, as a tumor suppressor in CCA via the PI3K/AKT pathway, might be a promising therapeutic target or prognostic marker for CCA.

scholarly journals Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

Proliferation and repair of guinea pig tracheal epithelium after neuropeptide depletion and injury in vivo

1997 ◽  
Vol 273 (6) ◽  
pp. L1235-L1241 ◽  
Author(s):  
John S. Kim ◽  
Valerie S. McKinnis ◽  
Kimberly Adams ◽  
Steven R. White
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Nuclear Antigen ◽  
Airway Epithelial ◽  
Epithelial Cell Proliferation ◽  
Injury Site ◽  
And Migration

Neuropeptides stimulate airway epithelial cell proliferation and migration in vitro, but the role of neuropeptides in the repair of the epithelium after injury in vivo is not clear. We studied epithelial proliferation and repair in 83 male Hartley guinea pigs. Animals received capsaicin weekly for 3 wk to deplete airway neuropeptides. One week later, the dorsal aspect of the trachea was injured with a metal stylette. Animals were killed 1 h to 1 wk later, after which epithelial cell proliferation was assessed for the presence of proliferating cell nuclear antigen (PCNA). PCNA labeling was <3% in noninjured animals. PCNA labeling increased substantially in the first 72 h after injury in control animals but was significantly decreased in capsaicin-treated animals within and adjacent to the site of injury. PCNA labeling increased opposite to the injury site in both control and capsaicin animals over the first 72 h. We conclude that neuropeptide depletion significantly attenuates both epithelial cell proliferation and repair in the first 72 h after mechanical injury to the trachea. However, neuropeptide depletion did not slow the ultimate repair of tracheal mucosal injury. Proliferation of epithelial cells in response to injury occurs throughout the airway, even away from the injury site.

Effect of cabazitaxel on the growth of human castration-refractory prostate cancer cells in vitro compared to docetaxel and on the anti-tumor properties of the angio-inhibitor PEDF in vivo.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 205-205
Author(s):  
Thomas Nelius ◽  
Courtney Jarvis ◽  
Dalia Martinez-Marin ◽  
Stephanie Filleur
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Cell Lines ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Raw264.7 Macrophages

205 Background: Docetaxel/DTX and cabazitaxel/CBZ have shown promise in the treatment of metastatic Castration-Refractory Prostate Cancer/mCPRC however, comparative studies are missing. Toxicities of these drugs are significant, urging the need to modify taxane regimens. Recently, low-dose metronomic/LDM treatments using conventional chemotherapeutic drugs have shown benefits in CPRC in improving the effect of anti-angiogenic agents. Previously, we have demonstrated that LDM-DTX in combination with PEDF curbs significantly CRPC growth, limits metastases formation and prolongs survival in vivo. In this study, we intended to compare the cytotoxic effect of CBZ and DTX on CRPC cells in vitro and CL1 tumors in vivo. Methods: PC3, DU145 cell lines were from ATCC.CL1 cells were obtained from androgen-deprived LNCaP cells. Cell proliferation was assessed by crystal violet staining and cell cycle analyses. In vitro cytotoxicity assays were performed on CL1 cells/RAW264.7 macrophages co-cultures treated with PEDF and increasing doses of taxanes. For the in vivo studies, CL1 cells were engineered to stably express the DsRed Express protein +/- PEDF. PEDF anti-tumor effects were assessed on s.c. xenografts treated with DTX (5mg/kg ip ev. 4 day) as reference, CBZ (5mg/kg ip ev. 4 days, 1mg/kg for 10 days, 0.5mg/kg q.a.d. and 0.1mg/kg daily) or placebo. Results: CBZ limits cell proliferation with a greater efficacy than DTX in all CRPC cell lines tested. DU145 presented the largest difference. High doses of taxane blocked tumor cells in mitosis, whereas LDM increased the SubG1 population. This effect was significantly higher in DU145 cells treated with CBZ. In vivo, 5mg/kg CBZ delayed tumor growth more efficiently than 5mg/kg DTX. PEDF/5mg/kg CBZ markedly delayed tumor growth compared to all treatments. Finally, engulfment of tumor cells by macrophages was higher in combined treatments suggesting an inflammation-related process. Conclusions: CBZ is more efficient than DTX both in vitro and in vivo.The data also reinforce PEDF as a promising anti-neoplasic agent in combination with LDM taxane chemotherapies.

scholarly journals Characterization and Evaluation of Two Novel Fluorescent Sigma-2 Receptor Ligands as Proliferation Probes

2011 ◽  
Vol 10 (6) ◽  
pp. 7290.2011.00009 ◽  
Author(s):  
Chenbo Zeng ◽  
Suwanna Vangveravong ◽  
Lynne A. Jones ◽  
Krzysztof Hyrc ◽  
Katherine C. Chang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Plasma Membrane ◽  
Mononuclear Cells ◽  
In Vivo Studies ◽  
Ki 67 ◽  
Peripheral Blood Mononuclear ◽  
Fluorescent Intensity ◽  
Fluorescent Markers

We synthesized and characterized two novel fluorescent sigma-2 receptor selective ligands, SW120 and SW116, and evaluated these ligands as potential probes for imaging cell proliferation. Both ligands are highly selective for sigma-2 receptors versus sigma-1 receptors. SW120 and SW116 were internalized into MDA-MB-435 cells, and 50% of the maximum fluorescent intensity was reached in 11 and 24 minutes, respectively. In vitro studies showed that 50% of SW120 or SW116 washed out of cells in 1 hour. The internalization of SW120 was reduced ≈30% by phenylarsine oxide, an inhibitor of endocytosis, suggesting that sigma-2 ligands are internalized, in part, by an endocytotic pathway. Subcellular localization studies using confocal and two-photon microscopy showed that SW120 and SW116 partially colocalized with fluorescent markers of mitochondria, endoplasmic reticulum, lysosomes, and the plasma membrane, suggesting that sigma-2 receptors localized to the cytoplasmic organelles and plasma membrane. SW120 did not colocalize with the nuclear dye 4′,6-diamidino-2-phenylindole. In vivo studies showed that the uptake of SW120 in solid tumors and peripheral blood mononuclear cells of mice positively correlated with the expression level of the cell proliferation marker Ki-67, suggesting that sigma-2 fluorescent probes may be used to image cell proliferation in mice.

scholarly journals Preparation nanoparticles of β-cyclodextrin loaded Scutellarein anti-tumor activity research by targeting integrin αvβ3

2021 ◽  
Author(s):  
JUNDONG WANG ◽  
TIANHAO LI ◽  
CHAOCHI YUE ◽  
SEN ZHONG ◽  
XIANGDONG YANG ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Water Solubility ◽  
Integrin Αvβ3 ◽  
Human Colon ◽  
In Vivo Studies ◽  
Human Colon Cancer ◽  
Proliferation And Apoptosis

Abstract BackgroundThe problems associated with poor water solubility of anticancer drugs are one of the most important challenges in achieving effective cancer therapy. The present study was designed to evaluate the effect of Scutellarein on human colon cancer cells in vitro by using a target αvβ-3 novel Scutellarein (Scu)-loaded niosome nanoparticle (β-CD-CL-Scu-cRGD).Resultsβ-CD-CL-Scu-cRGD has a diameter of 140.2nm and a zeta potential of -11.3 mV with a constant physicochemical stability. The MTT assay showed both Scu and β-CD-CL-Scu-cRGD caused a decrease in cell proliferation and viability of HT29, but β-CD-CL-Scu-cRGD showed better activity in vitro. Colony formation assay and flow cytometry assay showed that β-CD-CL-Scu-cRGD has a better effect on cell proliferation and apoptosis.ConclusionsAlthough further in vivo studies are necessary, our results suggested that β-CD-CL-Scu-cRGD could be an outstanding carrier to deliver Scu for potential therapeutic approaches into colon cancer.

scholarly journals CircTP63 Promotes Cell Proliferation and Invasion by Regulating EZH2 via Sponging miR-217 in Gallbladder Cancer

2021 ◽  
Author(s):  
Shouhua Wang ◽  
Huanjun Tong ◽  
Tingting Su ◽  
Di Zhou ◽  
Weibin Shi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Progression ◽  
Gallbladder Cancer ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ezh2 Expression ◽  
Proliferation And Invasion

Abstract Background: Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis in patients with GBC. CircRNA TP63 (circTP63) has been implicated in some tumor proliferation and invasion in some tumors. The study aims to investigate the clinical significance and functional role of circTP63 in GBC.Methods: The expression of circTP63 in GBC was detected by qRT-PCR and the association between circTP63 expression and prognosis of GBC patients was analyzed. CCK8 assay, flow cytometry analysis, transwell assay and in vivo studies were used to evaluated the cell proliferation and invasion after circTP63 knockdown in GBC cells. Luciferase reporter assays and RNA pull-down assay were used to determine the correlation between circTP63 and miR-217. Besides, western blot analysis was also performed.Results: In the present study, we showed that circTP63 expression was upregulated in GBC tissues and cells. Higher circTP63 expression was associated with lymph node metastasis and short overall survival (OS) in patients with GBC. In vitro, knockdown of circTP63 inhibited cell proliferation, cell cycle progression, migration and invasion in GBC. Besides, we demonstrated that knockdown of circTP63 inhibited GBC cell EMT process. In vivo, knockdown of circTP63 inhibited tumor growth in GBC. Mechanistically, we demonstrated that circTP63 competitively bind to miR-217 and promoted EZH2 expression and finally facilitated tumor progression.Conclusions: Our findings demonstrated that circTP63 sponge miR-217 and regulated EZH2 expression and finally facilitates tumor progression. Thus, targeting circTP63 may be a therapeutic strategy for the treatment of GBC.

scholarly journals Doxorubicin-induced myocardial failure in rats with malignant neoplasm: Protective role of fullerenol C60(OH)24

2008 ◽  
Vol 62 (3) ◽  
pp. 197-204 ◽  
Author(s):  
Rade Injac ◽  
Aleksandar Djordjevic ◽  
Borut Strukelj
Keyword(s):  
Untreated Control ◽  
Malignant Neoplasm ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Untreated Control Group ◽  
Cardiac Damage

The therapeutic utility of the anthracycline antibiotic doxorubicin is limited due to its cardiotoxicity. Our aim was to investigate the efficacy of fullerenol C60(OH)24 in preventing single, high-dose doxorubicin-induced cardiotoxicity in rats with malignant neoplasm. In vitro and in vivo studies have shown that fullerenol C60(OH)24, has strong antioxidative potential. Experiment was performed on adult female Sprague Dawley rats with chemically induced mammary carcinomas. All 32 rats (2-5 groups) received i.p. applications of 1-methyl-l-nitrosourea (MNU; 50 mg/kg body weight) on the 50th and 113th day of age. Animals were randomly divided into five groups as follows: (1) Untreated control group - rats received saline only; (2) Cancer control group - rats received MNU and saline; (3) Dox group - rats received MNU and Dox 8 mg/kg; (4) Full/Dox group -rats received MNU and Full 100 mg/kg 30 min before Dox 8 mg/kg; (5) Full group - rats received MNU and Full 100 mg/kg. Tumor incidence was 4.94 +- 0.576 per rat. The animals were sacrificed 2 days after the application of doxorubicin and/or fullerenol, and the serum activities of CK, LDH and ?-HBDH, as well as the levels of MDA, GSH, GSSG, GSH-Px, SOD, CAT, GR and TAS in the heart, were determined. The results obtained from the enzymatic activity in the serum show that the administration of a single dose of 8 mg/kg in all treated groups induces statistically significant damage. There are significant changes in the enzymes of LDH and CK (p < 0.05), after an i.p. administration of doxorubicin/fullerenol and fullerenol. Comparing all groups with untreated control group, point to the conclusion that in the case of a lower oc-HBDH/LDH ratio, results in more serious the liver parenchymal damage. The results revealed that doxorubicin induced oxidative damage and that the fullerenol antioxidative influence caused significant changes in MDA, GSH, GSSG, GSH-Px, SOD, CAT, GR and TAS level in the heart (p < 0.05). Ultra structural analysis of heart tissues from rats treated with doxorubicin and indicated that the hearts of the rats were protected from doxorubicin-induced subcellular damage. Doxorubicin/fullerenol rats did not appear to show significant cardiac damage although occasional focal loss of cristae in the mitochondria was observed. Therefore, it is suggested that fullerenol might be a potential cardioprotector in doxorubicin-treated individuals.

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