scholarly journals Linoleic Acid Upregulates Microrna-494 to Induce Quiescence in Colorectal Cancer

2021 ◽  
Vol 23 (1) ◽  
pp. 225
Author(s):  
Ruiko Ogata ◽  
Shiori Mori ◽  
Shingo Kishi ◽  
Rika Sasaki ◽  
Naoya Iwata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Linoleic Acid ◽  
Liver Metastases ◽  
Cancer Cells ◽  
Term Treatment ◽  
Colorectal Cancer Cell Line ◽  
Syngeneic Mouse ◽  
Cancer Dormancy ◽  
Long Term Treatment

Cancer dormancy is a state characterized by the quiescence of disseminated cancer cells, and tumor recurrence occurs when such cells re-proliferate after a long incubation period. These cancer cells tend to be treatment resistant and one of the barriers to successful therapeutic intervention. We have previously reported that long-term treatment of cancer cells with linoleic acid (LA) induces a dormancy-like phenotype. However, the mechanism underpinning this effect has not yet been clarified. Here, we investigate the mechanism of LA-induced quiescence in cancer cells. We first confirmed that long-term treatment of the mouse colorectal cancer cell line CT26 with LA induced quiescence. When these cells were inoculated subcutaneously into a syngeneic mouse and fed with an LA diet, the inoculated cancer cells maintained the quiescent state and exhibited markers of dormancy. LA-treated CT26 cells showed reduced oxidative phosphorylation, glycolysis, and energy production as well as reduced expression of the regulatory factors Pgc1α and MycC. MicroRNA expression profiling revealed that LA induced an upregulation in miR-494. The expression of Pgc1α and MycC were both induced by an miR-494 mimic, and the LA-induced decrease in gene expression was abrogated by an miR-494 inhibitor. The expression of miR-494 was enhanced by the mitochondrial oxidative stress produced by LA. In a syngeneic mouse subcutaneous tumor model, growth suppression by an LA diet and growth delay by LA pretreatment + LA diet were found to have similar effects as administration of an miR-494 mimic. In contrast, the effects of LA were abrogated by an miR-494 inhibitor. Analysis of human colorectal cancer tissue revealed that miR-494 was present at low levels in non-metastatic cases and cases with simultaneous liver metastases but was expressed at high levels in cases with delayed liver metastases, which also exhibited reduced expression of PGC1α and MYCC. These results suggest that miR-494 is involved in cancer dormancy induced by high levels of LA intake and that this microRNA may be valuable in targeting dormant cancer cells.

scholarly journals Oxaliplatin for Metastatic Colon Cancer in a Patient with Renal Failure

2008 ◽  
Vol 2 ◽  
pp. CMO.S412
Author(s):  
Kenji Katsumata ◽  
Tetsuo Sumi ◽  
Tatehiko Wada ◽  
Yasuharu Mori ◽  
Masayuki Hisada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Renal Failure ◽  
Term Treatment ◽  
Pharmacokinetic Data ◽  
Metastatic Colon Cancer ◽  
Standard Regimen ◽  
Long Term Treatment ◽  
Before And After ◽  
Cecal Cancer

Objective Oxaliplatin, a key part of the standard regimen for colorectal cancer in Western countries, has become available in Japan. In a hemodialysis patient with cecal cancer, we investigated the efficacy, safety, pharmacokinetics, and dialysability of oxaliplatin. Methods A 65-year-old man who had cecal cancer was treated with oxaliplatin (40 mg/m2) and l-leucovorin(l-LV) (200 mg/m2), which were administered simultaneously over 120 min via the side and main arms of a Y-tube, respectively. Then 5-FU (400 mg/m2) was administered rapidly via the side tube, followed by 5-FU (2,000 mg/m2) over 46 hours via the main tube. The patient had chronic renal failure due to diabetic nephropathy and hemodialysis was performed 3 times a week. Blood samples were collected from the dialyzer before and after each hemodialysis session to examine platinum clearance. Results The patient received 3 courses of oxaliplatin before he died of cancer. During hemodialysis, the platinum level fell from 0.32 μg/mL to 0.15 μg/mL. Conclusion Since patients with renal failure have various associated disorders and oxaliplatin has a long half-life, it is necessary to obtain more pharmacokinetic data to investigate its accumulation and dialysability during long-term treatment. Such data will assist in treating the rapidly increasing number of hemodialysis patients with colorectal cancer.

scholarly journals Negative Regulation of PTEN by MicroRNA-221 and Its Association with Drug Resistance and Cellular Senescence in Lung Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Ning Wang ◽  
Chen Zhu ◽  
Ye Xu ◽  
Wenliang Qian ◽  
Min Zheng
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Term Treatment ◽  
Lung Cancer Cells ◽  
Akt Pathway ◽  
Long Term Treatment ◽  
Important Regulator

Objective.Chemotherapy is the routine method for treating many cancers, but long-term treatment may result in developing resistance to the drugs. The aim of this study was to identify whether noncoding RNAs play a role in drug resistance and how they affect drug resistance.Materials and Methods.The expression levels of miR-221 in different lung cancer cell lines H226, H1299, and A549 were measured. H1299 and A549 cell lines were transfected to overexpress and downexpress miR-221, and cell viability and cell senescence were determined. The PTEN/Akt pathway was then examined by real-time polymerase chain reaction and Western blot analysis.Results. MiR-221 together with proteins MDR1 and ABCG2 was upregulated in Cisplatin-resistant A549 lung cancer cells. Anti-miR-221 inhibits proliferation and induces senescence in lung cancer cells. PTEN/Akt pathway axis was identified as a target of drug resistance induced by miR-221.Conclusion. Our results revealed that miR-221 is an important regulator for chemotherapy sensitivity and showed miR-221 as a potential target for drug sensitization.

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