CD133⁺/ABCC5⁺ cervical cancer cells exhibit cancer stem cell properties

This study explores the correlation between Forkhead box M1 (FOXM1) and ATP-binding cassette subfamily C member 5 (ABCC5) in relation to paclitaxel resistance in cervical cancer. It aims to identify potential cervical cancer stem cell markers, offering fresh perspectives for developing therapeutic strategies to overcome paclitaxel chemoresistance in cervical cancer.

Paclitaxel-resistant Hela cells (Hela/Taxol) were developed by intermittently exposing Hela cells to progressively increasing concentrations of paclitaxel. We assessed the biological properties of both Hela and Hela/Taxol cells using various assays: cell proliferation, clonogenic, cell cycle, apoptosis, scratch, and transwell. To determine which markers better represent tumor stem cells, we analyzed various known and potential stem cell markers in combination. Flow cytometry was employed to measure the proportion of positive markers in both parental and drug-resistant cell lines. Following statistical analysis to establish relative stability, CD133+ABCC5+ cells were sorted for further examination. Subsequent tests included sphere-forming assays and Western blot analysis to detect the presence of the stem cell-specific protein Sox2, aiding in the identification of viable cervical cancer stem cell markers.

The Hela/Taxol cell line exhibited significantly enhanced proliferation, migration, and invasion capabilities compared to the Hela cell line, alongside a marked reduction in apoptosis rates (P < 0.01). Notably, proportions of CD44⁺, CD24⁺CD44⁺, ABCC5+, CD24⁺CD44+ABCC5+, CD44+ABCC5+, CD24⁺CD44+FOXM1+, CD44+FOXM1+, CD133+ABCC5+, and CD133+FOXM1+ were significantly higher (P < 0.05). Furthermore, the size and number of spheres formed byCD133+ABCC5+ cells were greater in the sorted Hela/Taxol line (P < 0.01), with increased expression of the stem cell marker Sox2 (P < 0.001).

The Hela/Taxol cells demonstrate increased tumoral stemness, suggesting that CD133+ABCC5+ may serve as a novel marker for cervical cancer stem cells.