CANCER CHEMOPREVENTION BY METFORMIN HYDROCHLORIDE COMPARED TO PLACEBO IN ORAL POTENTIALLY MALIGNANT LESIONS: A RANDOMIZED CLINICAL TRIAL

Abstract

Background: The aim of the present randomized controlled clinical trial was to provide further molecular evidence for the postulated cancer chemopreventive potential of systemic Metformin hydrochloride on oral potentially malignant disorders (OPMDs), shown by simultaneous work by our team.

Subjects and methods: Forty non diabetic patients, suffering from oral potentially malignant lesions, namely leukoplakia and oral lichen planus, were retrieved from the outpatient clinic of Oral Medicine and Oral Diagnosis Department and the Diagnostic Center, Faculty of Dentistry, Cairo University, Egypt. The trial was conducted with two arms parallel groups, with each group consisting of 20 patients. One group received Metformin hydrochloride at a single daily dose of 500 mg, the other received a placebo. Recommended standard health and dental care was given to both groups and risk factors were eliminated. Clinical data, toluidine blue test, biopsies, immunohistochemical staining with cyclin­A2, tissue and salivary miRNA­31 and miRNA-210 levels evaluation, were all performed at baseline and at 3 months point.

Results: there was significant decrease of the lesion size in Metformin group while there was significant increase of the lesion size in placebo group (P-value < 0.05).

When compared to placebo, Metformin proved to affect the cell cycle-dependent mechanisms and epigenetic factors that could affect the progression of oral potentially malignant lesions, particularly with its ability to decrease Cyclin­A2 expression (P-value= 0.016), to down-regulate miRNA­31 and miRNA 210 levels (in both tissues and saliva). Changes in toluidine blue staining intensity, however, was not statistically significant.

Conclusions: Our results supported the other clinical trial by our team, showing that Metformin can offer a cancer chemopreventive effect in OPMDs, as it was capable of reducing significantly the size of the lesions and the degree of epithelial dysplasia together with down expression of Cyclin A­2 and cancer associated miRNA­31 and miRNA-210, which gave additional molecular validity for the concomitant results.