الفهرس 
Introduction and Aim of the workOnly 14 pages are availabe for public view
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Abstract
This study aims to inhibit the growth of Ehrlich cancer cells by activating a long- term quiescence or senescence state in these cells through the treatment with a triple combination regimen that involves a single dose of cisplatin and subsequent doses of metformin and sodium selenite.At the beginning of this study, 120 mice were divided into eight groups (15 mice/group). One group was left as a normal healthy group and injected intraperitoneally by 200 μL saline solution for 14 days. The other seven groups were inoculated intraperitoneally with 2.5×106 EAC cells.In this study, the promising experimental model of safe triple combination therapy was able to stop the growth and metastasis of EAC cells during their last stages (malignant ascites) and to survive as long as possible. The regimen of just one dose of cisplatin and later doses of metformin then sodium selenite could drive EAC cells from quiescence to senescence. Based on this, there was no tumor development over a long period of 100 days. The role of metformin and cisplatin in the combination was to induce quiescence by downregulation of mTOR and upregulation of p21 while sodium selenite transferred the tumor cells to senescence by partial downregulation of p21 and strong activation of mTOR.The previous finding was supported by studying the effect of one dose cisplatin and later doses of sodium selenite or metformin on EAC cells progression. Both dual therapies induced a long-term EAC quiescence, this confirmed by arresting cells in G0 phase which interpreted the delay in tumor development. They also promoted the adhesiveness of EAC cells via inhibition of ΔNp63 level in EAC cells. The matter caused development of solid tumors instead of a malignant ascites in EAC-bearing mice and extended the survival time of the treated mice.