Abstract：
:We have investigated in the current study, the possible modulatory effects of dexamethasone on cisplatin cytotoxicity in Ehrlich ascites carcinoma (EAC)-bearing female Swiss albino mice. Cisplatin (3.5mg/kg) was injected IP for 3 consecutive days in mice previously inoculated SC with EAC cells in the right flank. Dexamethasone (2.5mg/kg) was administered SC alone or 24h ahead of cisplatin challenge, and these regimens were given for 3 consecutive days. Dexamethasone enhanced the anti-tumor effects of cisplatin, clearly demonstrated by the increased mean tumor growth time (TGT) and tumor growth delay time (TGDT) values compared to cisplatin alone. The effects of dexamethasone on tumor angiogenesis and cell cycle distribution of EAC cells have been addressed as possible mechanisms, whereby the glucocorticoid could probably augment cisplatin cell-kill. Indeed, dexamethasone enhanced the angiostatic activity of cisplatin by 52.5%. The glucocorticoid also synchronized the EAC cells in the G2/M phase, secondary to its regulatory role on the transcriptional and translational activity in these cells, thus, exposing them to the dramatic cytotoxic potential of cisplatin. One could conclude that dexamethasone enhanced the anti-tumor effects of cisplatin via augmenting its angiostatic activity and modulating cell cycle kinetics. Also, dexamethasone did not alter cisplatin-induced nephrotoxicity, thus demonstrating an improved therapeutic potential.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Arafa HM,Abdel-Hamid MA,El-Khouly AA,Elmazar MM,Osman AMdoi
10.1016/j.tox.2006.02.007keywords:
subject
Has Abstractpub_date
2006-05-01 00:00:00pages
103-13issue
1-2eissn
0300-483Xissn
1879-3185pii
S0300-483X(06)00099-0journal_volume
222pub_type
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