Similar to our findings, CDDP reduced tumour growth when used alone

Discussion selleck The concentration of oxygen in human tumors widely varies, and it is not uncommon to find areas with oxy gen pressure lower than 2. 5 mmHg, and the extent of hypoxia seems to be tumor stage and size independent. Radiotherapy and conventional chemotherapies are often less effective in oxygen depressed cells. There fore it is of great importance to make use of the oxygen deprivation and find drugs that are more effective in hypoxic tumor cells. In our study the untreated hypoxic and anoxic ACHN and U 937 cells, as well as anoxic A2780 cells were less proliferative than corresponding normoxic cells. Indeed re sults also showed that ACHN and anoxic A2780 were more resistant to most drugs under reduced oxygen pressure, which is expected in view of the fact that slow proliferating tumor cells are less sensitive to chemotherapy.<br><br> Interestingly the reversed effect could be observed in H69, where oxygen deprived cells appeared more viable and was a lot more sensitive to drugs. MCF 7 cells were also Lenalidomide TNF-alpha 受容体 阻害剤 more sensitive to drugs in an oxygen deprived envir onment but, in difference to H69, the MCF 7 cells displayed no proliferative difference in normoxic and hypoxic or anoxic surroundings. Hypoxia mostly occurs in tumors and therefore different cell lines with a solid tumor origin were the most interesting objects in this study. The leukemic lymphoma cell line U 937 is not a solid tumor per se, but was included in the study for comparison. Un treated U 937 cells were less viable in an oxygen deprived environment, but did not display any real difference in sen sitivity to chemotherapy in hypoxia or anoxia.<br><br> Three drugs were more effective in a hypoxic and anoxic environment, cisplatin, mitomycin c and tirapazamine. Earlier studies have revealed LY2228820 分子量 contradictive results, showing hypoxic cells to be more resistant to cisplatin in some cell lines but also showing cisplatin to be a HIF 1 inhibitor. Mitomycin c was also clearly more effective in most of the oxygen deprived cell lines. Hypoxia induces the enzymatic system capable of activating mitomycin c and is therefore considered more toxic to hypoxic cells. However, mitomycin c has also been shown to be less effective in hypoxic testicular germ cell tumor cell lines and was in our study less effective in ACHN under hypoxic and anoxic conditions.<br><br> Tirapazamine was signifi cantly more effective in all oxygen deprived cell lines, and our results for tirapazamine highly correspond to previous studies of this bioreductive prodrug. Tirapazamine is activated under hypoxic conditions by a reductase enzyme, in which creating a highly reactive molecule that in turn causes single and double strand breaks in the DNA of tumor. The drugs with increased resistance in hypoxic and anoxic cells were docetaxel, irinotecan, melphalan and sorafenib. Docetaxel has been shown to both influence and not influence the HIF 1 protein accumu lation. Although this study proposed that docetaxel was associated with increased drug resistance in most cells in anoxia and hypoxia, other studies has implied that some cell lines was not. In accordance to this study, irinotecan has earlier been shown to be less effective under hypoxic conditions.