scholarly journals Acquired resistance to decitabine and cross-resistance to gemcitabine during the long-term treatment of human HCT116 colorectal cancer cells with decitabine

2015 ◽  
Vol 10 (2) ◽  
pp. 761-767 ◽  
Author(s):  
MIKA HOSOKAWA ◽  
MAI SAITO ◽  
AIKO NAKANO ◽  
SAKURA IWASHITA ◽  
AYANO ISHIZAKA ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Acquired Resistance ◽  
Term Treatment ◽  
Cross Resistance ◽  
Long Term Treatment ◽  
Colorectal Cancer Cells

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 Sunitinib treatment promotes metastasis of drug-resistant renal cell carcinoma via TFE3 signaling pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Luchao Li ◽  
Shuo Zhao ◽  
Zhengfang Liu ◽  
Nianzhao Zhang ◽  
Shuo Pang ◽  
...  
Keyword(s):  
Renal Cell ◽  
Cell Cancer ◽  
Acquired Resistance ◽  
Resistant Cell ◽  
Term Treatment ◽  
Acquired Drug Resistance ◽  
Sunitinib Treatment ◽  
Long Term Treatment

AbstractReceptor tyrosine kinase (RTK) inhibitors, such as sunitinib and sorafenib, remain the first-line drugs for the treatment of mRCC. Acquired drug resistance and metastasis are the main causes of treatment failure. However, in the case of metastasis Renal Cell Cancer (mRCC), which showed a good response to sunitinib, we found that long-term treatment with sunitinib could promote lysosome biosynthesis and exocytosis, thereby triggering the metastasis of RCC. By constructing sunitinib-resistant cell lines in vivo, we confirmed that TFE3 plays a key role in the acquired resistance to sunitinib in RCC. Under the stimulation of sunitinib, TFE3 continued to enter the nucleus, promoting the expression of endoplasmic reticulum (ER) protein E-Syt1. E-Syt1 and the lysosomal membrane protein Syt7 form a heterodimer, which induces ER fragmentation, Ca2+ release, and lysosomal exocytosis. Lysosomal exocytosis has two functions: pumping sunitinib out from the cytoplasm, which promotes resistance to sunitinib in RCC, releasing cathepsin B (CTSB) into the extracellular matrix (ECM), which can degrade the ECM to enhance the invasion and metastasis ability of RCC. Our study found that although sunitinib is an effective drug for the treatment of mRCC, once RCC has acquired resistance to sunitinib, sunitinib treatment will promote metastasis.

Concomitant blockade of EGFR and MEK overcomes acquired resistance to anti-EGFR therapy in colorectal cancer cells and patients’ avatars.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 2626-2626 ◽  
Author(s):  
Alberto Bardelli ◽  
Sandra Misale ◽  
Sabrina Arena ◽  
Giulia Siravegna ◽  
Simona Lamba ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Acquired Resistance ◽  
Colorectal Cancer Cells
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