Volume 26, Issue 128, October 2022

Therapeutic effects of paclitaxel and nivolumab on cancer stem cells of experimentally induced oral squamous cell carcinoma

Ahmed Samir Zakaria^1♦, Mohamed Gomma Khalial², Asmaa Mohamed Zahran³, Mohamed Mahmoud Ahmed⁴, Emad Alqalshy⁵

¹Assistant lecturer, Oral and Dental Pathology department, Faculty of Dental Medicine, (Boys), Al-Azhar University, Assiut, Egypt
²Assistant Professor, Department of Oral and Dental Pathology, Faculty of Dental Medicine, (Boys), Al-Azhar University, Assiut, Egypt
³Professor, Department of Clinical pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
⁴Professor, and head of Oral and Dental Pathology department, Faculty of Dental Medicine, (Boys), Al-Azhar University, Cairo, Egypt
⁵Lecturer, Oral and Dental Pathology department, Faculty of Dental Medicine, (Boys), Al-Azhar University, Cairo, Egypt

^♦Corresponding author
Assistant lecturer, Oral and Dental Pathology department, Faculty of Dental Medicine, (Boys), Al-Azhar University, Assiut, Egypt

ABSTRACT

Purpose: The main objective of this research was directed to evaluate the therapeutic effect of paclitaxel and nivolumab on cancer stem cells (CSCs) of experimentally generated hamster buccal pouch (HBP) carcinoma. Methods: 50 hamsters were grouped into five groups. GI: animals left untreated. GII: animals were painted with 7, 12-dimethylbenz (a) anthracene (DMBA) thrice a week. GIII: following DMBA application, animals injected intraperitoneally (IP) with nivolumab on days 7, 10 and 13. GIV: animals were treated with paclitaxel (IP), twice a week and metformin (IP), thrice a week. GV: animals were receiving a combination of nivolumab, paclitaxel and metformin. Following euthanization, right pouches were surgically excised, bisected with one section fixed and processed for H&E and immunohistochemical (IHC) examinations, and other section of the fresh tissue was used for evaluation by flow cytometric (FCM). Results: Gross observation histopathological, and IHC changes were recorded. By FCM, CD44+/CD24- and CD44+/CD24+ were detected. The results indicated that the CD44+/CD24- cells percentage in GI, GII, GIII, GIV and GV were 0.005%, 1.33%, 0.25%, 0.26% and 0.17%, respectively. While the CD44+/CD24+ cells percentage in GI, GII, GIII, GIV and GV was 0.001%,0.11%, 0.05%, 0.03% and 0.02%, respectively. Apoptosis of CSC, in GI, GII, GIII, GIV and GV was 26.5%, 1.7 %, 38.1 %, 23.2% and 53.6% respectively. Regarding apoptosis of all cancer cells, the percentage of apoptotic cells is 1.72%, 24.5%, 54.2%, 48.3 and 68.3%, respectively. Conclusions: Combination of paclitaxel and nivolumab has the capability to suppress tumor development and induction of apoptosis in both CSC oral squamous cell carcinoma (OSCC) and non-CSC OSCC.

Keywords: Cancer stem cells; HBP carcinoma; Paclitaxel; Nivolumab

Medical Science, 2022, 26, ms425e2405

PDF

DOI: https://doi.org/10.54905/disssi/v26i128/ms425e2405

Published: 24 October 2022