Differential response of lung cancer cell lines to vitamin D derivatives depending on EGFR, KRAS, p53 mutation status and VDR polymorphism

Impact of calcitriol and an AKT inhibitor, AT7867, on survival of rat C6 glioma cells

“…The increase in the VDR expression level was found as a physiological response against the inducer calcitriol treatment. Additionally, our finding of cell survival inhibition was in consistence with the prior studies [10,16,17,19,20]. On the other hand, ˜2-fold decrease in VDR gene expression as a response to 10 µmol/L AT7867, a potential inhibitor of AKT, suggests that there may be a relationship between vitamin D and AKT pathway.…”

“…These wide effects of vitamin D are driven through its receptor VDR, which also acts as a transcription factor [5,13]. Recent clinical studies revealed the association of differential expressional patterns of vitamin D with various cancer types [16,17,19,20,[31][32][33]. Indeed, preclinical studies have shown that calcitriol or its analogues might have potential therapeutic effect as an anticancer agent [5-8, 13, 15, 34].…”

“…Another important factor in cellular progression of glioblastoma is the downstream pathways and the gene variations of epidermal growth factor receptor (EGFRvIII), a tyrosine kinase protein [19,20] which is a major survival pathway activated in various types of cancer. Amongst EGFRvIII activated signaling pathways, phosphatidylinositol-3-kinase (PI3K)/serine-threonine protein kinase (AKT) pathway plays a pivotal role on the cell survival.…”

“…Amongst EGFRvIII activated signaling pathways, phosphatidylinositol-3-kinase (PI3K)/serine-threonine protein kinase (AKT) pathway plays a pivotal role on the cell survival. In fact, EGFRvIII preferentially signals through the PI3K/AKT-1 pathway [19,21,22]. Phosphorylation of AKT-1 by PI3K activation regulates various cellular mechanisms including proliferation, cell-survival, cell growth and angiogenesis.…”

Alternative approaches to target Myc for cancer treatment

“…113 Either the genomic backgrounds of cell lines and mouse models or the serum-free treatment in the viability test of Omomyc would inevitably lead to an intensified macropinocytosis. The NCSLC cell lines (H1299, H1975, and A549) used to justify the uptake of Omomyc harbor NRAS, 114 EGFR, 115 and KRAS 116 mutation, respectively. These mutations could trigger downstream actin remodeling for macropinocytosis initiation and enhance macropinocytosis in diverse cell lines.…”