The suppressing effects of BTG3 expression on aggressive behaviors and phenotypes of colorectal cancer: Anin vitroandvivostudy

Abstract

Here, we found that down-regulated expression of BTG3 might be positively correlated with colorectal carcinogenesis and its overexpression suppressed proliferation, glycolysis, mitochondrial respiration, cell cycle progression, migration, and invasion, and induced apoptosis, senescence and differentiation in SW480 and SW620 cells. After treated with cisplatin, MG132, paclitaxel and SAHA, BTG3 transfectants exhibited lower viability and higher apoptosis than the control in both time- and dose-dependent manners. BTG3 overexpression up- regulated the protein expression of Cyclin E, p16, p27, NF-κB, p38α/β, XIAP, Bcl-2, ATG14 and p53, but down-regulated the mRNA expression of MRP1, BCRP, and mTOR in SW480 and SW620 cells. BTG3 overexpression inhibited tumor growth of SW620 cells by suppressing proliferation and inducing apoptosis. It was suggested that down-regulated BTG3 expression might be considered as a marker for colorectal carcinogenesis. BTG3 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of colorectal cancer.

Cucurbitacin B inhibits cell proliferation and induces cell apoptosis in colorectal cancer by modulating methylation status of BTG3

“…Our previous study and other reports have demonstrated that BTG3 overexpression suppresses cell proliferation and promotes apoptosis in CRC, epithelial ovarian cancer and esophageal adenocarcinoma [37][38][39][40]. These evidences demonstrate that BTG3 exerts anti-proliferative and pro-apoptotic effects in CRC and other human cancers.…”

The clinicopathological significances and related signal pathways of BTG3 mRNA expression in cancers: A bioinformatics analysis

“…Lv et al (2018) found that BTG3 knockdown promoted cell proliferation, migration, invasion, relieved G 2 arrest, and inhibited apoptosis in colorectal cancer cells with PAK2 (p21 activated kinase 2), RPS6KA5 (ribosomal protein S6 kinase A5), YWHAB (tyrosine 3-monooxygenase/ tryptophan 5-monooxygenase activation protein beta), and STAT3 up-regulated and RAP1A (ras-related protein rap-1A), DUSP6 (dual specificity phosphatase 6), and STAT (signal transducer and activator of transcription) 1 down-regulated. Our group demonstrated that BTG3 expression inhibited proliferation, tumor growth, migration and invasion, and induced autophagy, apoptosis, and chemosensitivity to cisplatin, MG132 (proteasome inhibitor), paclitaxel, and SAHA (histone deacetylase inhibitor) in gastric and colorectal cancer cells (Gou et al, 2015;Zheng et al, 2017). In esophageal adenocarcinoma cells, BTG3 upregulation suppressed the proliferation and invasion (Du et al, 2015).…”

“…In addition, BTG3 mRNA expression was positively linked to the differentiation of gastric cancer, in line with our previous report about gastric cancer tissues (Gou et al, 2015). BTG3 was also reported to induce the differentiation of gastric and colorectal cancer cells, evidenced by a higher level of alkaline phosphatase (Gou et al, 2015;Zheng et al, 2017). These findings suggested that BTG3 mRNA expression might underlie the molecular mechanisms of gastric cancer differentiation.…”

“…In our previous work, BTG3 overexpression was demonstrated to reverse the aggressive phenotypes of gastric and colorectal cancer cells (Gou et al, 2015;Zheng et al, 2017). Here, we aimed to clarify the clinicopathological and prognostic significances, and related signal pathways of BTG3 mRNA expression in cancers by a bioinformatics analysis.…”

“…Deng et al (2013) demonstrated that BTG3 expression was negatively associated with a higher incidence of metastasis, a better differentiation, longer disease-free time, and overall survival time of epithelial ovarian cancer as an independent factor of prognosis. However, there was no relationship between BTG3 protein expression and overall survival rates of the patients with gastric (Gou et al, 2015) or colorectal (Zheng et al, 2017) cancer. In the present study, the positive correlation between BTG3 mRNA expression and survival rate was seen in gastric and breast cancer patients, but not for lung and ovarian cancers according to Kaplan-Meier plotter.…”