1) Background: The aim of the present study was directed to investigate the effect of imiquimod and bevacizumab on cancer stem cell(s) (CSC(s)) of induced hamster buccal pouch (HBP) carcinoma; 2) Methods: 50 syrian male hamsters were divided into 5 group(s) (G(s)),10 each. While the animals in GI (negative control) were, left untreated for 19 weeks (ws), the right pouches of those in (GII- GV) were painted with 7,12-dimethylbenz (a) anthracene (DMBA), 3times a week for 14 ws. After that, the animals in GII (positive control) were left with no additional treatment for other 5 ws (total period 19 ws), whereas those in GIII were painted with imiquimod once daily for other 4 ws, then, after other week (total period 19 ws) the animals were euthanized. Those in GIV were injected intraperitoneally (IP) with bevacizumab (10mg/kg / once daily for a week), then, after other week (total period 16 ws) the animals were euthanized and those in GV were painted with imiquimod and IP injection with bevacizumab with doses and administration method similar to those introduced in single treatments then, after other week (total period 19 ws) the animals were euthanized. After termination of the experiment, gross observations and tumor volume were recorded, then, the animals were euthanized, and all right pouches were surgically excised, prepared, fixed and processed for hematoxylin and eosin (H&E) stain examination for recording histopathological features including the depth of invasion (DOI) and immunohistochemical (IHC) staining utilizing B-lymphoma moloney murine insertion region (BMI-1) stem cell marker and vascular endothelial growth factor (VEGF) antibody.; 3) Results: : tumor volume recorded highly significant difference (p value < 0.001) between GIII, GIV or GV and GII. Histopathological findings revealed DOI with highly significant difference (p value < 0.001) between GIII, GIV or GV and GII. BMI-1 and VEGF antibodies revealed highly significant difference (p-value < 0.001) between GV and the following; GIII and GIV consequently. In contrast, BMI-1 had non-significant difference (p-value < 0.125) between GIII and GIV, while VEGF had highly significant difference (p-value < 0.001) between GIII and GIV; 4) Conclusion: bevacizumab could inhibit tumor vasculature-VEGF expression. Imiquimod could inhibit CSCs-BMI-1 expression. Combination of imiquimod-bevacizumab has an inhibitory effect on carcinoma cell and cancer stem cells in HBP SCC.

HBP carcinoma; imiquimod; bevacizumab; CSCs.