scholarly journals Metformin increases chemo-sensitivity via gene downregulation encoding DNA replication proteins in 5-Fu resistant colorectal cancer cells

Oncotarget ◽  
2017 ◽  
Vol 8 (34) ◽  
pp. 56546-56557 ◽  
Author(s):  
Sung-Hee Kim ◽  
Soon-Chan Kim ◽  
Ja-Lok Ku
Keyword(s):  
Colorectal Cancer ◽  
Dna Replication ◽  
Cancer Cells ◽  
Replication Proteins ◽  
Colorectal Cancer Cells

scholarly journals HNRNPLL stabilizes mRNA for DNA replication proteins and promotes cell cycle progression in colorectal cancer cells

2018 ◽  
Vol 109 (8) ◽  
pp. 2458-2468 ◽  
Author(s):  
Keiichiro Sakuma ◽  
Eiichi Sasaki ◽  
Kenya Kimura ◽  
Koji Komori ◽  
Yasuhiro Shimizu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Dna Replication ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Replication Proteins ◽  
Cycle Progression ◽  
Colorectal Cancer Cells

scholarly journals Efficacy of the MEK Inhibitor Cobimetinib and its Potential Application to Colorectal Cancer Cells

2018 ◽  
Vol 47 (2) ◽  
pp. 680-693 ◽  
Author(s):  
Shu Gong ◽  
Dongsheng Xu ◽  
Jialin Zhu ◽  
Fangdong Zou ◽  
Rui Peng
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Dna Replication ◽  
Cancer Therapy ◽  
Cell Viability ◽  
Cancer Cells ◽  
Mek Inhibitor ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
Hct116 Cells

Background/Aims: Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells. Methods: HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real-time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues. Results: We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity of cobimetinib in HCT116 cells. Notably, cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer. Conclusions: Our results suggest the potential use of cobimetinib in colorectal cancer therapy.

scholarly journals Expression profiling of colorectal cancer cells reveals inhibition of DNA replication licensing by extracellular calcium

2017 ◽  
Vol 1864 (6) ◽  
pp. 987-996 ◽  
Author(s):  
Abhishek Aggarwal ◽  
Herbert Schulz ◽  
Teresa Manhardt ◽  
Martin Bilban ◽  
Rajesh V Thakker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Replication ◽  
Cancer Cells ◽  
Expression Profiling ◽  
Extracellular Calcium ◽  
Colorectal Cancer Cells
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