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.