Evaluation of the Growth Suppressing and Stemness Inhibiting Effect of Cisplatin and 5 Fluorouracil on Human Epithelial Squamous Cell Carcinoma (HEp-2)

Abstract

An increasing area of research interest in the field of cancer is a subpopulation of cells that have been implicated in tumor sustainability and cancer relapse - cancer stem cells - owing to the striking similarities between them and normal stem cells. In this study, we investigated the apoptosis inducing and stemness inhibiting potential of cisplatin and 5-fluorouracil on the resistant human epithelial squamous cell carcinoma (HEp-2). HEp2 cells were made resistant to 5-fluorouracil and cisplatin by exposing them to low concentration of 5-fluorouracil and cisplatin for 1 month. The resistant cells were assayed for DNA Fragmentation, apoptosis, and induction of stemness. The IC50 of the drugs on the resistant cells were 11.92µg/mL and 1954µg/mL for cisplatin and 5-fluorouracil respectively. The gene expression profiles show the upregulation of p21as well as stemness genes, SOX2 and OCT4, decreased expression of p53 and BAX in 5 fluorouracil treated cells and an increased expression of BCL2 in cisplatin treated cells. We conclude that pluripotency in these cells is maintained through expression of OCT4 and SOX2 via p21. Hence, the upregulation of p21 may contribute to the mechanism of resistance in Hep2 cells. The findings of this present study lend credence to the possibilities of modulating stemness properties in resistant cells. Future studies should explore the role of more chemotherapy drugs on stemness of a wide range of cancer cells whose increased proliferation is enhanced by cancer stem cells.