Evaluation on the IGF-IR Inhibitor CP-751,871, alone and in combination with paclitaxel in lung and colon cell lines

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22125-e22125 ◽  
Author(s):  
R. Garcia-Carbonero ◽  
M. T. Agullo-Ortuño ◽  
F. Lopez-Rios ◽  
C. V. Diaz-Garcia ◽  
A. Cortijo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Flow Cytometric Analysis ◽  
Colon Cancer Cell ◽  
Sequential Treatment ◽  
Flow Cytometric ◽  
Colon Cancer Cell Lines

e22125 Background: Signaling through the insulin-like growth factor 1 receptor (IGF-IR) has been implicated in the resistance to a number of clinically relevant anti-cancer agents. The aim of this study was to assess the direct anti-tumour effects of CP-751,871, alone and in combination with paclitaxel in lung and colon cancer cell lines. Methods: Four lung and four colon cancer cell line where treated with the IGF-IR inhibitor CP-751,871 and/or Paclitaxel in simultaneous or sequential treatments. Response to treatments was evaluated by WST-1 cell survival assays. Flow cytometric analysis was used to estimate the effect on the cell cycle and apoptosis. IGF-IR mRNA expression was determined by quantitative real-time PCR and relative gene expression values were calculated by the ΔΔCt method. Results: No correlation between basal IGF-IR mRNA expression and CP-751,871 response was observed in cell lines tested. Flow cytometric analysis demonstrated that CP-751,871 enhanced cell cycle arrest at the G1/G0 checkpoint with minimal effects on apoptosis. Combined simultaneous and, more strongly, sequential treatment with CP- 751,871 and Paclitaxel showed improved response in cell growth inhibition on HCC78, H1299, Colo205 and HT29 cell lines, and was statistically superior to Paclitaxel alone (p< 0.001) and CP-751,871 alone (p< 0.001). In H460, LS180 and DLD-1 cell lines, concomitant, but no sequential treatment resulted in antagonistic interactions. Conclusions: CP-751,871 showed a modest anti-tumour activity, predominantly cytostatic, against lung and colon cancer cell lines, that is not related to the mRNA expression. CP-751,871 tends to enhance the effects of paclitaxel in vitro, depending on sequence of administration and on the model system used. No significant financial relationships to disclose.

scholarly journals β-Lapachone Inhibits Lung Metastasis of Colorectal Cancer by Inducing Apoptosis of CT26 Cells

2016 ◽  
Vol 16 (4) ◽  
pp. 585-596 ◽  
Author(s):  
Ji-Ye Kee ◽  
Yo-Han Han ◽  
Jinbong Park ◽  
Dae-Seung Kim ◽  
Jeong-Geon Mun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Experimental Metastasis ◽  
Colon Cancer Cell Lines ◽  
Metastasis Model

Background: β-Lapachone is a quinone-containing compound found in red lapacho ( Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. Methods: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription–polymerase chain reaction were performed to examine the effects of β-lapachone on metastatic phenotypes and molecular mechanisms. The effect of β-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. Results: We found that the inhibition of proliferation of the colon cancer cell lines by β-lapachone was due to the induction of apoptosis and cell cycle arrest. β-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of β-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, β-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, β-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, β-lapachone significantly inhibited the lung metastasis of CT26 cells. Conclusions: Our results demonstrated the inhibitory effect of β-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.

scholarly journals MicroRNA silencing of CNN1 and CNN2 protein family members regulates biology processes in colorectal cancer by targeting the p53 signal pathway

2020 ◽  
Author(s):  
Fuda Huang ◽  
Mingwei Wei ◽  
Anmin Wang ◽  
Ya Zhang ◽  
Zebang Qin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Expression Levels ◽  
Colon Cancer Cell Lines ◽  
Cancer Tissues

Abstract BackgroundCalponin was first defined as a striated muscle troponin T-like protein that binds actin thin filaments to regulate smooth muscle contraction. There are few studies of CNN1 and CNN2 in colorectal cancer, and the roles these two genes play in colorectal cancer cell lines and the mechanisms by which they act are unknown.MethodsWe used immunohistochemistry to identify expression of the two genes in the cancer tissues. RT-PCR was used to measure expression levels of microRNA. W performed western blots to measure changes in signaling pathways in the context of expression interference.Meanwhile, the same method was used to measure binding relationship between the two genes and key pathway proteins. To determine the relationship between microRNA and gene mRNA, we used the reporter gene method. We used the chi-square and t-test methods to analyze the significance and correlations of the data.Results and conclusionsExpression levels of CNN1 were lower in colon cancer tissues than in normal mucosal tissues. After downregulating CNN1, the cell cycle in colon cancer cell lines progressed quickly, and the expression of related pathway proteins also increased. Expression levels of CNN2 were higher in colon cancer tissues, and its downregulation significantly inhibited cell cycle progression in colon cancer cell lines. We confirmed correlations between the expression of microRNA and CNN2 using data analysis.Bars indicate ± standard errors.*p < 0.05; **p < 0.01 compared with the control. The inhibition of the expression of CNN2 mRNA using microRNA was confirmed using western blot. The combination of the two at the mechanism level was also demonstrated using the reporter gene method.

scholarly journals SLC7A5 Promotes Colorectal Cancer Progression by Regulating Cell Cycle and Migration

2021 ◽  
Author(s):  
Baiyou Tang ◽  
Lihua Zhang ◽  
Jing Yu ◽  
Mingjing Peng ◽  
Yu Cheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Functional Enrichment ◽  
Public Database ◽  
Colon Cancer Cell Lines

Abstract Background: Solute carrier family 7 member 5 (SLC7A5) was identified highly expressed and as a key participant in various tumor development; however, the role it played in colorectal cancer remains unclear. Methods and Results: In the current study, the expression of SLC7A5 were systematically mined in public databases and validated by real-time PCR in colon cancer and normal tissues. And then, the co-expression and pathway analysis got from public database, which indicated the potential influence of SLC7A5 for the etiology of colorectal cancer, were evaluated in the colon cancer cell lines by loss of SLC7A5 function experiment, flow cytometry, western blot, and wound healing assay. The results showed that the mRNA expression of SLC7A5 was significantly higher in colorectal cancer tissues than that in the non-tumor controls for GEO and TCGA datasets as well as 40 pairs of Xiangya clinical samples. The functional enrichment analysis based on public database showed that the pathways enriched most were cell cycle and epithelial-to-mesenchymal transition (EMT), and Cyclin D1 (CCND1) were the only gene that had a significant positive correlation with SLC7A5. Loss of SLC7A5 function in colon cancer cell lines could arrest cell cycle at G1 phase by down-regulating CCND1 and CDK2 protein expression, and may reduce cell migration by reversing EMT though upregulation of E-Cadherin and downregulation of zonula occludens-1. Conclusion: SLC7A5 is likely associated with the progression of colon cancer.

scholarly journals Silencing LRH-1 in colon cancer cell lines impairs proliferation and alters gene expression programs

2015 ◽  
Vol 112 (8) ◽  
pp. 2467-2472 ◽  
Author(s):  
James R. Bayrer ◽  
Sridevi Mukkamala ◽  
Elena P. Sablin ◽  
Paul Webb ◽  
Robert J. Fletterick
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Colon Cancer Cell Lines ◽  
A Cell

Colorectal cancers (CRCs) account for nearly 10% of all cancer deaths in industrialized countries. Recent evidence points to a central role for the nuclear receptor liver receptor homolog-1 (LRH-1) in intestinal tumorigenesis. Interaction of LRH-1 with the Wnt/β-catenin pathway, highly active in a critical subpopulation of CRC cells, underscores the importance of elucidating LRH-1’s role in this disease. Reduction of LRH-1 diminishes tumor burden in murine models of CRC; however, it is not known whether LRH-1 is required for tumorigenesis, for proliferation, or for both. In this work, we address this question through shRNA-mediated silencing of LRH-1 in established CRC cell lines. LRH-1 mRNA knockdown results in significantly impaired proliferation in a cell line highly expressing the receptor and more modest impairment in a cell line with moderate LRH-1 expression. Cell-cycle analysis shows prolongation of G0/G1 with LRH-1 silencing, consistent with LRH-1 cell-cycle influences in other tissues. Cluster analysis of microarray gene expression demonstrates significant genome wide alterations with major effects in cell-cycle regulation, signal transduction, bile acid and cholesterol metabolism, and control of apoptosis. This study demonstrates a critical proproliferative role for LRH-1 in established colon cancer cell lines. LRH-1 exerts its effects via multiple signaling networks. Our results suggest that selected CRC patients could benefit from LRH-1 inhibitors.

scholarly journals Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3091
Author(s):  
Euna Jeong ◽  
Yejin Lee ◽  
Youngju Kim ◽  
Jieun Lee ◽  
Sukjoon Yoon
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Large Scale ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Transcriptional Networks ◽  
Colon Cancer Cell Lines

The availability of large-scale, collateral mRNA expression and RNAi data from diverse cancer cell types provides useful resources for the discovery of anticancer targets for which inhibitory efficacy can be predicted from gene expression. Here, we calculated bidirectional cross-association scores (predictivity and descriptivity) for each of approximately 18,000 genes identified from mRNA and RNAi (i.e., shRNA and sgRNA) data from colon cancer cell lines. The predictivity score measures the difference in RNAi efficacy between cell lines with high vs. low expression of the target gene, while the descriptivity score measures the differential mRNA expression between groups of cell lines exhibiting high vs. low RNAi efficacy. The mRNA expression of 90 and 74 genes showed significant (p < 0.01) cross-association scores with the shRNA and sgRNA data, respectively. The genes were found to be from diverse molecular classes and have different functions. Cross-association scores for the mRNA expression of six genes (CHAF1B, HNF1B, HTATSF1, IRS2, POLR2B and SATB2) with both shRNA and sgRNA efficacy were significant. These genes were interconnected in cancer-related transcriptional networks. Additional experimental validation confirmed that siHNF1B efficacy is correlated with HNF1B mRNA expression levels in diverse colon cancer cell lines. Furthermore, KIF26A and ZIC2 gene expression, with which shRNA efficacy displayed significant scores, were found to correlate with the survival rate from colon cancer patient data. This study demonstrates that bidirectional predictivity and descriptivity calculations between mRNA and RNAi data serve as useful resources for the discovery of predictive anticancer targets.

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