ART1 Silencing Enhances Apoptosis of Mouse CT26 Cells via the PI3K/Akt/NF-κB Pathway

Abstract

Background/Aims: Colorectal carcinoma is one of the most common cancers world-wide, with high morbidity and mortality rates. Arginine ADP-ribosyltransferase 1(ART1) is an important ecto-ADP-ribose transferase and has been proven to be intimately involved in a number of biological processes. However, the influence of ART1 on survival and apoptosis of colorectal carcinoma cells and the potential mechanism of action of ART1 remain uncharacterized. Methods: ART1 was silenced via lentiviral vector-mediated short hairpin RNA (shRNA) in CT26 colon carcinoma cells, and cisplatin (CDDP) was applied to induce apoptosis. Survival and apoptosis rate of CT26 cells was assessed by CCK8 assay, flow cytometry and Hoechst 33342 staining. Expression and activity of signaling proteins were detected by Western blot. Results: ART1 knockdown enhanced the inhibition of cell survival and increased the apoptosis induced by CDDP. Furthermore, the reduced survival rate correlated with reduced levels of phos-Akt^Thr308 and phos-IκBa and reduced NF-κB p65 nuclear translocation. A decline in Bcl-2 and Bcl-xl expression and an increase in Bax expression may explain the enhanced apoptosis. Conclusion: This study provides a molecular mechanism for the function of ART1 in colorectal carcinoma and defines a potential therapeutic target for the enhanced treatment of this prominent world-wide disease.

Effect of ART1 on the proliferation and migration of mouse colon carcinoma CT26 cells in vivo

“…A previous study (11) has shown that ART1 expression was increased in colorectal cancer and has a positive correlation with the expression of vascular endothelial growth factor (VEGF), which suggests that it may have an association with tumor angiogenesis. It has also been observed that the silencing of ART1 in CT26 cells may inhibit the proliferation of cells by restraining cell cycle at the G0/G1 phase, suppressing matrix adhesion and migration in vitro (12–14). However, whether the changes of ART1 in CT26 cells are able to affect the proliferation and invasion in vivo has yet to be fully elucidated.…”

Dihydroartemisinin Accentuates the Anti-Tumor Effects of Photodynamic Therapy via Inactivation of NF-κB in Eca109 and Ec9706 Esophageal Cancer Cells

“…It is known that Bcl-2, which is a target of NF-κB, is involved in protection from apoptosis [22]. It has been demonstrated that some agents can activate NF-κB and stimulate Bcl-2 gene promoter activity in the MIA-PaCa-2 human pancreatic cancer cell line [23].…”

Expression of ADP-ribosyltransferase 1 Is Associated with Poor Prognosis of Glioma Patients

“…These substrate proteins are involved in cell proliferation, angio- genesis, and inflammation (Zolkiewska and Moss 1995;Jones and Baird 1997;Saxty et al 2001;Paone et al 2002). Moreover, the ART1 expression has been reported to be upregulated in human colorectal carcinoma and hepatocellular carcinoma, and silencing ART1 in CT26 colon adenocarcinoma cells can significantly inhibit cell proliferation and promote cell apoptosis Xiao et al 2013;Su et al 2014). The functions of ART1 may include various pathways including the ERK and AKT signaling, as well as the integrin and poly (ADP-ribose) polymerase (PARP-1) signaling Xiao et al 2013Xiao et al , 2015.…”

“…Moreover, the ART1 expression has been reported to be upregulated in human colorectal carcinoma and hepatocellular carcinoma, and silencing ART1 in CT26 colon adenocarcinoma cells can significantly inhibit cell proliferation and promote cell apoptosis Xiao et al 2013;Su et al 2014). The functions of ART1 may include various pathways including the ERK and AKT signaling, as well as the integrin and poly (ADP-ribose) polymerase (PARP-1) signaling Xiao et al 2013Xiao et al , 2015. In our studies, RT-qPCR analysis indicated that the mRNA expression level of ART1 in glioma was higher than that in normal brain tissues, and we found that the positive expression of ART1 was closely correlated with highergrade of glioma and can serve as an independent predictor for the poorer prognosis of glioma patients.…”