Seen against this cancer cell line SW480. 5-FU and SN 38 reported that their function through the induction of S-phase of the cell cycle, w During oxaliplatin exerts its function through the trailer Ufung of cells in G2 / M. Since hypoxic cells led to his arrest on G0/G1 phase, with a consequent inhibition of cell growth, then put the inhibitory effect of 5-FU and oxaliplatin Hesperidin inhibitor is not completely ndig be exercised under hypoxia. The analysis of apoptosis showed that the treatment carried out with 5-FU under normoxia to an increase Hten rate of apoptosis that was inhibited by hypoxia. In Similar manner, the apoptosis induced by oxaliplatin under normoxia was inhibited by hypoxia. Under normoxia, SN entered treatment and 38 Born erh Hte apoptosis, but it was not significantly affected by hypoxia.
Thus, the hypoxic environment significantly abolished the inhibitory effect of 5-FU and GSK2126458 1086062-66-9 oxaliplatin, but not of SN 38, on human cancer cells, c Lon-dependent Ngigen cell cycle arrest in the G0 phase / G 1 and inhibition of apoptosis. Then, to investigate the mechanisms of Ph Phenomena, we focused on HIF, which reported that in the acquisition of resistance to therapy, including radiotherapy and chemotherapy should be included. Various mechanisms have been involved in chemoresistance induced by HIF-1, including the induction of an anti-apoptotic and arrest cells in G0/G1 phase. Our data showed an accumulation of HIF in cells cultured in hypoxia, which was not affected by treatment with 5-FU and oxaliplatin.
Interestingly, however, the treatment of these cells entered with SN 38 A dose-born Independent inhibition of the accumulation of HIF first The cells HIF accumulate 1 are less sensitive to apoptotic signals per, in part by the inhibition of B-cell agonist lymphoma2 Homologiedom Ne 3 interact death Dom ne, the B-cell lymphoma 2 protein is associated with death explained rt B-cell lymphoma, and 2 X-associated proteins. This is consistent with our findings that treatment with 5-FU and oxaliplatin, which leads not affect the accumulation of HIF 1, to an inhibition of pro-apoptotic effect in comparison to cells cultured under normoxia, but not for cells that SN 38, which deals with the accumulation of HIF-1 inhibits. The rate of apoptosis was similar in both cells treated with SN 38 under normoxia and those treated under hypoxia.
The G0/G1 cell cycle arrest induced by hypoxia was also reported to be dependent Be ngig HIF-1, which inhibits cyclin D1 and induces p21 and p27. So it makes sense that SN 38, the anti-apoptotic effect of hypoxia via a HIF-1-dependent Ngigen d way Mpft. Topoisomerase I inhibitors such as topotecan and SN 38 were reported to inhibit HIF-1 expression in malignant gliomas. SN 38 has been shown to inhibit VEGF expression through inhibition of HIF-1 in glioma cells and therefore to prevent endothelial proliferation and tube formation. In colorectal tumors, a combination treatment with rapamycin, which are known HIF target is 1, and irinotecan, which is to inhibit the ability to prevent the accumulation of HIF-1 shown to induce massive death of cells c cancer lon under hypoxic but not normoxic, conditions in vitro and a dramatic reduction in tumor volume in vi