scholarly journals TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guoqiong Lei ◽  
Sushun Liu ◽  
Xin Yang ◽  
Chao He
Keyword(s):  
Colon Cancer ◽  
Cancer Cell ◽  
Cell Model ◽  
P53 Protein ◽  
Underlying Mechanism ◽  
Resistant Cell ◽  
Colon Cancer Cell ◽  
Mutant P53 ◽  
Ht29 Cells ◽  
First Choice

Background. Oxaliplatin is the first-choice chemotherapy method for patients with advanced colon cancer. However, its resistance leads to treatment failure for many patients. In our experiments, we aim to elucidate the associations among TRIM29 protein, mutant P53, and the resistance of colon cancer cells to oxaliplatin. Methods. HCT116 and HT-29 cells were cultured and transfected with plasmids pIRES2-ZsGreen1-TRIM29-flag. Western blot and real-time qRT-PCR were utilized to examine the protein and mRNA expressions of TRIM29 and other related markers, respectively. MTT assay was utilized to determine the cell growth rate and generate the inhibition curve. Continuous culture in low-concentration oxaliplatin was conducted to construct oxaliplatin-resistant cell lines. The coimmunoprecipitation method and immunofluorescence detection were used to examine the interaction between TRIM29 and mutant P53 protein in HT29 cells. Results. We successfully transfected pIRES2-ZsGreen1-TRIM29-flag into HCT116 and HT29 cells, which were utilized in the whole experiments. TRIM29 significantly increased the sensitivity of P53 mutant colon cancer cell HT29 to oxaliplatin. The oxaliplatin-resistant model of P53 mutant colon cancer cell HT29 was successfully constructed. TRIM29 physically bound with mutant P53 and retained it in the cytoplasm from the nucleus, which inhibited its transcription function of downstream genes such as MDR1. In addition, TRIM29 successfully reversed the resistance of HT29-OX resistant cell model to oxaliplatin. Conclusion. In mutant P53 colon cancer cell HT29, TRIM29 greatly increased the sensitivity of HT29 to oxaliplatin and reverse oxaliplatin resistance. The underlying mechanism is TRIM29 may increase the sensitivity of HT29 to oxaliplatin by blocking the transcriptional function of mutant P53, which inhibits the transcription function of its downstream gene such as MDR1.

scholarly journals hCAIX Expression and Cell Cycle in Cytokine Stimulated Human Colon Cancer Cells

2019 ◽  
Author(s):  
Rahsan Ilikci Sagkan ◽  
Feray Kockar ◽  
Ali Sengul ◽  
Sukran Yilmaz ◽  
Ugur Musabak
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Colon Carcinoma ◽  
Cancer Cell ◽  
Cell Model ◽  
Hot Spot ◽  
Colon Cancer Cell ◽  
Expression Level ◽  
Colon Cells ◽  
Ht 29

Abstract Background: At the aim of this study, we investigated the effects of different kind of cytokines and the combinations of which on human carbonic anhydrase IX ( hCAIX) expression in HT-29 cell selected as colon carcinoma model for different doses and time of exposure to determine role of cytokines for treatment of colon carcinoma cells. Results: To sum up, h CA9 expression in the levels of gene and protein increased in HT-29 cells when stimulated with 1000 U/mL TGF-β for 24 h. The stimulation of HT-29 cells with IL1 α alone and IL1α- TGF-β combination has not revealed any effect on hCA9 expression in both levels of gene and protein in contrast to, 1000 U/mL IL1α-TNFα and especially TGFβ-TNFα have reducing effect on h CA9 expression level in HT-29 cells for time ranges of 24 h, 48 h, 72 h. In addition to this data, it was observed that HT-29 cells at the phase of G0G1 are arrested in cell cycle when stimulated with either of 1000 U/mL IL1α-TNFα and TGFβ-TNFα. Moreover, it was observed that h CA9 expression level in HT-29 cells decreases at the phases of synthesis (S) and G2M. Discussion: We concluded that combination of TNFα-TGFβ has created antagonistic effect on hCA9 expression in HT-29 colon cancer cell model. On the other hand, combination of TNFα-IL1α caused sinergistic effect on h CA9 expression level in this cell model. When these results are demonstrated decrease in the cytokine exposed hCA9 expression is a finding to develop a novel approach for anticancer therapy. Conclusion: Our finding related to the change in the expression of hCA9 following cytokine stimulate to colon cancer cell line gives an idea about the effect of cytokine stimulation on the expression of this gene which will be a hot spot research in colon carcinogenesis. Methods: HT-29 colon cells were chosen as a colorectal adenocarcinoma model. hCA9 gene expression in the level of mRNA was measured in cytokines stimulated HT-29 cells by Quantitative Real-time PCR. Meanwhile, hCAIX expression in the level of protein and cell cycle aassay were detected by flow cytometry.

scholarly journals The therapeutic effect of the BRD4-degrading PROTAC A1874 in human colon cancer cells

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
An-cheng Qin ◽  
Hua Jin ◽  
Yu Song ◽  
Yun Gao ◽  
Yi-Fan Chen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
P53 Protein ◽  
Cell Activity ◽  
Colon Cancer Cell ◽  
Protein Stabilization ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer

Abstract A1874 is a novel BRD4-degrading proteolysis targeting chimera (PROTAC). In primary colon cancer cells and established HCT116 cells, A1874 potently inhibited cell viability, proliferation, cell cycle progression, as well as cell migration and invasion. The BRD4-degrading PROTAC was able to induce caspase and apoptosis activation in colon cancer cells. Furthermore, A1874-induced degradation of BRD4 protein and downregulated BRD-dependent genes (c-Myc, Bcl-2, and cyclin D1) in colon cancer cells. Significantly, A1874-induced anti-colon cancer cell activity was more potent than the known BRD4 inhibitors (JQ1, CPI203, and I-BET151). In BRD4-knockout colon cancer cells A1874 remained cytotoxic, indicating the existence of BRD4-independent mechanisms. In addition to BRD4 degradation, A1874 cytotoxicity in colon cancer cells was also associated with p53 protein stabilization and reactive oxygen species production. Importantly, the antioxidant N-acetyl-cysteine and the p53 inhibitor pifithrin-α attenuated A1874-induced cell death and apoptosis in colon cancer cells. In vivo, A1874 oral administration potently inhibited colon cancer xenograft growth in severe combined immuno-deficient mice. BRD4 degradation and p53 protein elevation, as well as apoptosis induction and oxidative stress were detected in A1874-treated colon cancer tissues. Together, A1874 inhibits colon cancer cell growth through both BRD4-dependent and -independent mechanisms.

Thymidylate synthase inhibition triggers apoptosis via caspases-8 and -9 in both wild-type and mutant p53 colon cancer cell lines

2003 ◽  
Vol 39 (9) ◽  
pp. 1310-1317 ◽  
Author(s):  
H.H.J Backus ◽  
D Wouters ◽  
C.G Ferreira ◽  
V.M.M van Houten ◽  
R.H Brakenhoff ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Thymidylate Synthase ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Mutant P53 ◽  
Wild Type ◽  
Colon Cancer Cell Lines

scholarly journals NMR Profiling of Ononis diffusa Identifies Cytotoxic Compounds against Cetuximab-Resistant Colon Cancer Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3266
Author(s):  
Vittoria Graziani ◽  
Nicoletta Potenza ◽  
Brigida D’Abrosca ◽  
Teresa Troiani ◽  
Stefania Napolitano ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Resistant Cell ◽  
Colon Cancer Cell ◽  
Partial Purification ◽  
Nmr Analysis ◽  
Ht 29

In the search of new natural products to be explored as possible anticancer drugs, two plant species, namely Ononis diffusa and Ononis variegata, were screened against colorectal cancer cell lines. The cytotoxic activity of the crude extracts was tested on a panel of colon cancer cell models including cetuximab-sensitive (Caco-2, GEO, SW48), intrinsic (HT-29 and HCT-116), and acquired (GEO-CR, SW48-CR) cetuximab-resistant cell lines. Ononis diffusa showed remarkable cytotoxic activity, especially on the cetuximab-resistant cell lines. The active extract composition was determined by NMR analysis. Given its complexity, a partial purification was then carried out. The fractions obtained were again tested for their biological activity and their metabolite content was determined by 1D and 2D NMR analysis. The study led to the identification of a fraction enriched in oxylipins that showed a 92% growth inhibition of the HT-29 cell line at a concentration of 50 µg/mL.

scholarly journals The Impact of Cetuximab Plus AKT- or mTOR- Inhibitor in a Patient-Derived Colon Cancer Cell Model with Wild-Type RAS and PIK3CA Mutation

2017 ◽  
Vol 8 (14) ◽  
pp. 2713-2719 ◽  
Author(s):  
Ju Sun Kim ◽  
Jung Eun Kim ◽  
Kyung Kim ◽  
Jeeyun Lee ◽  
Joon Oh Park ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cell ◽  
Mtor Inhibitor ◽  
Cell Model ◽  
Pik3ca Mutation ◽  
Colon Cancer Cell ◽  
Wild Type ◽  
The Impact

Expression of p53 protein in rat colon cancer cell lines transfected with Rous sarcoma virus-33

1997 ◽  
Vol 121 (2) ◽  
pp. 133-137
Author(s):  
Bella Sandler ◽  
Marta Grofova ◽  
Patricia Smirnoff ◽  
Rivka Zusman ◽  
Igor Zusman
Keyword(s):  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Rous Sarcoma Virus ◽  
P53 Protein ◽  
Colon Cancer Cell ◽  
Rat Colon ◽  
Rous Sarcoma ◽  
Colon Cancer Cell Lines ◽  
Sarcoma Virus

scholarly journals Association of Ozone with 5-Fluorouracil and Cisplatin in Regulation of Human Colon Cancer Cell Viability: In Vitro Anti-Inflammatory Properties of Ozone in Colon Cancer Cells Exposed to Lipopolysaccharides

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Vincenzo Simonetti ◽  
Vincenzo Quagliariello ◽  
Pierangela Giustetto ◽  
Marianno Franzini ◽  
Rosario Vincenzo Iaffaioli
Keyword(s):  
Colon Cancer ◽  
Cell Viability ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cell ◽  
Human Colon Cancer Cell ◽  
Human Colon Cancer ◽  
Cancer Management ◽  
Ht29 Cells ◽  
Anti Inflammatory

Introduction. Ozone therapy is an effective medical treatment for different diseases like mucositis, psoriasis, acute pain, neurovascular diseases, and cancer. The aim of this study is based on the association of different ozone concentration with 5-fluorouracil and cisplatin in human colon cancer cell (HT29 cell line) in order to investigate possible anticancer synergistic effects. Methods. HT29 cells were incubated with ozone at different concentration ranging from 10 up to 50 μg/ml at different incubation time alone or in combination with cisplatin and 5-fluorouracil. Cell viability was performed by using a modified MTT method. Anti-inflammatory studies were conducted incubating HT29 with or without 20, 30, or 50 μg/ml of ozone before exposure to lipopolysaccharides. Results. Ozone alone has a time and concentration dependent cytotoxicity against HT29 cells (IC50 at 24 h: 30 μg/ml). Association of ozone with drugs increases cytotoxicity by 15–20%. Preincubation of ozone at 50 μg/ml decreases IL-8, IL-6, and IL-1β production by 50, 56, and 70%, respectively, compared to untreated cells. Conclusion. These results indicated that ozone could be useful in colon cancer management in combination with 5-fluorouracil and cisplatin with significant inhibition of cytokines having a central role in colon cancer cell survival and chemoresistance.

The impact of cetuximab plus AKT- or mTOR- inhibitor in patient-derived colon cancer cell model with RAS wild type and PIK3CA mutation.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e15153-e15153
Author(s):  
Seung Tae Kim ◽  
Su Jin Lee ◽  
Joon Oh Park ◽  
Ho Yeong Lim ◽  
Won Ki Kang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cell ◽  
Mtor Inhibitor ◽  
Cell Model ◽  
Pik3ca Mutation ◽  
Colon Cancer Cell ◽  
Wild Type ◽  
The Impact
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