scholarly journals Noxa in colorectal cancer: a study on DNA, mRNA and protein expression

Oncogene ◽  
2003 ◽  
Vol 22 (30) ◽  
pp. 4675-4678 ◽  
Author(s):  
Agneta K Jansson ◽  
Anna M Emterling ◽  
Gunnar Arbman ◽  
Xiao-Feng Sun
2017 ◽  
Vol 42 (5) ◽  
pp. 1769-1778 ◽  
Author(s):  
Ran Ao ◽  
Lin Guan ◽  
Ying Wang ◽  
Jia-Ni Wang

Background/Aims: This paper aims to explore the effects of pyruvate kinase (PK) M2 gene silencing on the proliferation and apoptosis of colorectal cancer (CRC) LS-147T and SW620 cells. Methods: CRC LS-147T and SW620 cells highly expressing PKM2 were randomly selected by quantitative real-time polymerase chain reaction (qRT-PCR) and then assigned into the blank (no transfection), PKM2-shRNA (transfection with shRNA) and empty plasmid (transfection with empty plasmid) groups. Immunofluorescence was applied to detect PKM2 protein expression. qRT-PCR and Western blotting were conducted to assess mRNA and protein expression of PKM2, p53 and p21. The cell counting kit-8 (CCK-8) assay was used to assess cell proliferation. Flow cytometry was used to assess the cell cycle and apoptosis rate, and a senescence-associated β-galactosidase staining kit was used to assess cell senescence. Results: PKM2 exhibited high mRNA expression among CRC LS-147T and SW620 cells with remarkable protein expression noted in the cytoplasm and nucleus. The PKM2-shRNA group exhibited reduced PKM2 mRNA and protein expression, whereas p53 and p21 expression was increased compared with the blank and empty plasmid groups. Cell proliferation in PKM2-shRNA cells decreased significantly compared with the blank group and empty plasmid groups. The PKM2-shRNA group exhibited more cells in the G1 phase and fewer cells in the G2/M phase compared with the blank and empty plasmid groups. In addition, the PKM2-shRNA group exhibited significantly increased apoptosis rates and β-galactosidase activity compared with the blank and empty plasmid groups. Conclusion: Our study demonstrates that PKM2 gene silencing suppresses proliferation and promotes apoptosis in LS-147T and SW620 cells.


2018 ◽  
Vol 120 (2) ◽  
pp. 121-130 ◽  
Author(s):  
Cuiping Liu ◽  
Chen Chen ◽  
Fuguo Yang ◽  
Xin Li ◽  
Lixue Cheng ◽  
...  

AbstractPhytic acid (PA) has been demonstrated to have a potent anticarcinogenic activity against colorectal cancer (CRC). Defects of the intestinal mucosal barrier and inflammation processes are involved in the development and progression of CRC. In the present study, we evaluated the effect of PA on the intestinal mucosal barrier and proinflammatory cytokines. After a 1-week acclimatisation period, sixty Wistar male rats were divided into the following five groups, with twelve rats per group: the control group (CG), model group (MG), low-PA-dose group (0·25 g/kg per d), middle-PA-dose group (0·5 g/kg per d), and high-PA-dose group (1 g/kg per d). 1,2-Dimethylhydrazine (DMH) at a dosage of 30 mg/kg of body weight was injected weekly to induce CRC for 18 weeks. We examined the expression of genes related to the intestinal mucosal barrier in the model. The results demonstrated that tumour incidence was decreased following PA treatment. The mRNA and protein expression of mucin 2 (MUC2), trefoil factor 3 (TFF3) and E-cadherin in the MG were significantly lower than those in the CG (P<0·05). The mRNA and protein expression of claudin-1 in the MG were significantly higher than those in the CG (P<0·05). PA elevated the mRNA and protein expression of MUC2, TFF3 and E-cadherin, and diminished the mRNA and protein expression of claudin-1. Furthermore, PA decreased serum levels of proinflammatory cytokines, which included TNF-α, IL-1β and IL-6. In conclusion, this study suggests that PA has favourable effects on the intestinal mucosal barrier and may reduce serum proinflammatory cytokine levels.


2013 ◽  
Vol 36 (5) ◽  
pp. 411-419 ◽  
Author(s):  
Lars Henrik Jensen ◽  
Anders Aamann Rasmussen ◽  
Lene Byriel ◽  
Hidekazu Kuramochi ◽  
Dorthe Gylling Crüger ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Huang ◽  
Guihua Wang ◽  
Chunmei Zhao ◽  
Rong Geng ◽  
Shu Zhang ◽  
...  

Colorectal cancer (CRC) is a complex and heterogeneous disease with four consensus molecular subtypes (CMS1-4). LTBP2 is a member of the fibrillin/LTBP super family and plays a critical role in tumorigenesis by activating TGF-β in the CMS4 CRC subtype. So far, the expression and prognostic significance of LTBP2 in CRC remains obscure. In this study, we aimed to analyze the mRNA and protein expression levels of LTBP2 in CRC tissues and then estimate their values as a potential prognostic biomarker. We detected the mRNA expression of LTBP2 in 28 cases of fresh CRC tissues and 4 CRC cell lines and the protein expression of LTBP2 in 483 samples of CRC tissues, matched tumor-adjacent tissues, and benign colorectal diseases. LTBP2 protein expression was then correlated to patients’ clinical features and overall survival. Both LTBP2 mRNA and protein expression levels in CRC tissues were remarkably superior to those in adjacent normal colorectal tissues (P=0.0071 and P<0.001, respectively), according to TCGA dataset of CRC. High LTBP2 protein expression was correlated with TNM stage (P<0.001), T stage (P<0.001), N stage (P<0.001), and M stage (P<0.001). High LTBP2 protein expression was related to poor overall survival in CRC patients and was an independent prognostic factor for CRC. LTBP2 mRNA expression was especially higher in the CMS4 subtype (P<0.001), which was confirmed in CRC cell lines. Our data suggested that LTBP2 may act as an oncogene in the development of colorectal cancer and have important significance in predicting CRC prognosis. LTBP2 could be a novel biomarker and potential therapeutic target for mesenchymal colorectal cancer and can improve the outcome of high-risk CRC.


2011 ◽  
Vol 105 (2) ◽  
pp. 119-124 ◽  
Author(s):  
Yoon-Goo Kang ◽  
Chan-Kwon Jung ◽  
Ahwon Lee ◽  
Won-Kyung Kang ◽  
Seung-Taek Oh ◽  
...  

Author(s):  
Zahra Zare ◽  
Tina Nayerpour dizaj ◽  
Armaghan Lohrasbi ◽  
Zakieh Sadat Sheikhalishahi ◽  
Amirhooman Asadi ◽  
...  

Background: Metastasis of cancer cells is the primary responsible for death in patients with colorectal cancer (CRC). Transforming growth factor-β (TGF-β)-induced matrix metalloproteinases (MMPs) are essential for the metastasis process. Silibinin is a natural compound extracted from the Silybum marianum that exhibits anti-neoplastic activity in cancer cell lines. In this study, we evaluated the effects of silibinin on MMP-2 and MMP-9 induced by TGF-β in human HT-29 CRC cell line and the potential mechanism underlying the effects. Methods: The present in vitro study was done on the HT-29 cell line. The HT-29 cell line was cultured in RPMI1640 and exposed to TGF- β (5 ng/ml) in the absence and presence of different concentrations of silibinin (10, 25, 50, and 100 μM). The effect of silibinin on HT-29 cell viability was measured with the MTT assay. A real-time polymerase chain reaction (Real-Time PCR) determined the relative mRNA expression of MMP-2 and MMP-9. Western blotting was employed to examine MMP-2 and MMP 9 protein expression and Smad2 phosphorylation. Results: Silibinin inhibits cell viability of HT-29 cell line at 24 hours in a dose-dependent manner. TGF-β increased the mRNA and protein expression of MMP-2, MMP-9, and phosphorylated Smad2 compared to controls. Pharmacological inhibition with silibinin markedly blocked TGF-β–induced MMP-2 and MMP-9 mRNA and protein expression and Smad2 phosphorylation. Conclusion: Silibinin decreased the cell viability of HT-29 cancer cells in a dose-dependent manner. Silibinin also inhibited TGF-β-stimulated MMP-2 and MMP-9 expression in HT-29 cells, possibly mediated with the Smad2 signaling pathway.


Author(s):  
Tao Xie ◽  
Yao Li ◽  
Shi-Lei Li ◽  
Hai-Feng Luo

Although astragaloside IV exhibits anti-inflammation, immunoregulatory, and anticancer properties, the chemosensitization effects of astragaloside IV in colorectal cancer have never been reported. Our study tested whether astragaloside could increase cisplatin sensitivity in colorectal cancer. CCK-8 assay was used to measure the cell viability of colorectal cancer cells. Quantitative real-time PCR and Western blot were performed to determine the mRNA and protein expression, respectively. Our data revealed that astragaloside IV administration significantly suppressed the cell growth of colorectal cancer cells, whereas no obvious cytotoxicity of astragaloside IV was observed in nonmalignant colonic cells. In addition, combined treatment with astragaloside IV dramatically elevated the chemosensitivity of colorectal cancer cells to cisplatin. Mechanical investigation revealed that the mRNA and protein expression of NOTCH3 was significantly lower in cisplatin and astragaloside IV-treated cells compared with cells treated with cisplatin alone. On the contrary, no obvious changes in tumor cell growth were shown after upregulation of NOTCH3 whether in the presence or absence of astragaloside IV. Thus, our data demonstrate that astragaloside IV increases the chemosensitivity of colorectal cancer cells to cisplatin, at least partly, through inhibition of NOTCH3. This study suggests that combined therapy with astragaloside IV might be a novel therapeutic approach for colorectal cancer.


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