Document Type : Original Article


Division of Biochemistry, Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt



Background: Currently, combination therapy has become the cornerstone of cancer treatment. The combination of different anti-cancer mechanisms can induce tumor cell quiescence. However, toxicity to normal tissue is the major limitation of existing combined drugs.
Method: In this experimental study, Ehrlich ascites carcinoma inoculated into mice was targeted with just one dose of cisplatin and later doses of metformin, a safe anti-diabetic drug with an anti-cancer effect, to maintain Ehrlich ascites carcinoma (EAC) cells in the quiescent state and secure a longer survival time without tumor recurrence.
Results: The group that underwent dual therapy developed a delayed solid tumor instead of a malignant ascites. The induction of chemo-quiescence in the EAC cells was proven by the downregulation of mechanistic target of rapamycin and the upregulation of cyclin-dependent kinase inhibitor 1 (p21) expressions. Intriguingly, the conversion of free neoplastic cells into a solid tumor was associated with a significant decrease in ΔNp63 immunostaining in EAC cells.
Conclusion: Taken together, a single dose of cisplatin followed by metformin doses could overcome the aggressiveness of malignant ascites by the conversion into a solid tumor, induction of chemo-quiescence, and the extension of survival time.


This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.30476/mejc.2021.86035.1321