Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines

Olejniczak-Kęder, Agata; Szaryńska, Magdalena; Wrońska, Agata; Siedlecka-Kroplewska, Kamila; Kmieć, Zbigniew

doi:10.3892/ijo.2019.4809

Cited by 15 publications

(18 citation statements)

References 85 publications

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“…In the HT-29 cell line, we found that CTX monotherapy could neither reduce the proliferation of tumor cells, nor inhibit the cell cycle and induce apoptosis, and in the detection of molecule phosphorylation rates, we found that knockdown or overexpression of EGFR in HT-29 cells did not cause significant changes in the downstream molecule phosphorylation rates of EGFR. In a study on gold nanoparticles, CTX-loaded nanoparticles did not significantly cause apoptosis in HT-29 cells compared to unloaded nanoparticles (36), and in HT-29 cells, the application of anti-EGFR antibody alone could not change the tumor cell spheroidization size or proliferation rate (37). These results are consistent with our research.…”

Section: Discussionsupporting

confidence: 90%

A dual-targeted molecular therapy of PP242 and cetuximab plays an anti-tumor effect through EGFR downstream signaling pathways in colorectal cancer

Kong¹,

Qun²,

Mao³

et al. 2021

J Gastrointest Oncol

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Background: Epidermal growth factor receptor (EGFR) and its downstream Ras-mitogen-activated protein kinase kinase (MAPKK, MEK)-extracellular regulated protein kinase (ERK) signaling pathway and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway play important roles in the pathogenesis of colorectal cancer (CRC). The combination therapy of anti-EGFR and anti-mTOR needs to be explored.Methods: Here we combined the anti-EGFR monoclonal antibody cetuximab (CTX) with the mTOR inhibitor PP242 in CRC cell lines and mouse xenograft models and discussed the changes of EGFR downstream signaling pathways of CRC cell lines.Results: In HT-29 cells and Caco-2 cells, combined application of CTX and PP242 significantly inhibited the proliferation of CRC cells in vivo and in vitro. In BRAF wild-type Caco-2 cells, combined application of CTX and PP242 inhibited the activation of the EGFR and its downstream signaling pathways.Conclusions: Our research further demonstrates the effectiveness of the combined application of CTX and PP242 in inhibiting CRC cell lines from the perspective of cell proliferation, cell cycle, apoptosis, and mouse xenografts. We revealed that the combined application of CTX and PP242 can inhibit tumor growth and proliferation by inhibiting the phosphorylation of key molecules in EGFR downstream MEK-ERK and MEK 4/7 (MKK)-c-Jun N-terminal kinase (JNK) signaling pathways in BRAF wild-type CRC cells. In addition, we found that in BRAF mutant CRC cells, the monotherapy of PP242 resulted in negative feedback increased EGFR phosphorylation rates, accompanied by significant up-regulation of downstream MEK and ERK phosphorylation.

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Section: Discussionsupporting

confidence: 90%

A dual-targeted molecular therapy of PP242 and cetuximab plays an anti-tumor effect through EGFR downstream signaling pathways in colorectal cancer

Kong¹,

Qun²,

Mao³

et al. 2021

J Gastrointest Oncol

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“…A large number of studies confirmed that aspirin has a potential anti‐tumour effect; however, the application mechanisms underlying the application of aspirin combined with nano‐agents containing anti‐tumour drugs is not yet clear. Compared with the closest work related with aspirin in anti‐cancer treatment [36, 37], we used a novel nano‐drug delivery system to encapsulate both drugs and enhanced the cellular internalisation of drugs, thus showing higher uptake and increasing the therapeutic efficacy. In addition, we selected a non‐cytotoxic concentrations of aspirin (0.1 and 0.5 mM) to combine with 5‐Fu to evaluate its synergistic antitumour activity.…”

Section: Discussionmentioning

confidence: 99%

Chitosan nanoparticles loaded with aspirin and 5‐fluororacil enable synergistic antitumour activity through the modulation of NF‐κB/COX‐2 signalling pathway

Wang

Shen

Zhao

2020

IET nanobiotechnol.

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Based on the enhancement of synergistic antitumour activity to treat cancer and the correlation between inflammation and carcinogenesis, the authors designed chitosan nanoparticles for co-delivery of 5-fluororacil (5-Fu: an as anti-cancer drug) and aspirin (a non-steroidal anti-inflammatory drug) and induced synergistic antitumour activity through the modulation of the nuclear factor kappa B (NF-κB)/cyclooxygenase-2 (COX-2) signalling pathways. The results showed that aspirin at non-cytotoxic concentrations synergistically sensitised hepatocellular carcinoma cells to 5-Fu in vitro. It demonstrated that aspirin inhibited NF-κB activation and suppressed NF-κB regulated COX-2 expression and prostaglandin E2 (PGE2) synthesis. Furthermore, the proposed results clearly indicated that the combination of 5-Fu and aspirin by chitosan nanoparticles enhanced the intracellular concentration of drugs and exerted synergistic growth inhibition and apoptosis induction on hepatocellular carcinoma cells by suppressing NF-κB activation and inhibition of expression of COX-2.

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“…HT29 cells are human intestinal epithelial cells which produce the secretory component of immunoglobulin A (IgA) and carcinoembryonic antigen (CEA). HT29 cells are used for tumourigenicity studies [36,37]. HCT116 cells have been widely used in the study of biological characteristics of malignant tumor cells, the mechanism of anticancer drugs, and the screening of anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell

Lei

Liu

Yang

et al. 2021

Canadian Journal of Gastroenterology and Hepatology

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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.

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Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines

Cited by 15 publications

References 85 publications

A dual-targeted molecular therapy of PP242 and cetuximab plays an anti-tumor effect through EGFR downstream signaling pathways in colorectal cancer

A dual-targeted molecular therapy of PP242 and cetuximab plays an anti-tumor effect through EGFR downstream signaling pathways in colorectal cancer

Chitosan nanoparticles loaded with aspirin and 5‐fluororacil enable synergistic antitumour activity through the modulation of NF‐κB/COX‐2 signalling pathway

TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell

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