The Kinesin Eg5 Inhibitor K858 Enhances Radiosensitivity in Esophageal Squamous Cell Carcinoma and Affects the Expression of Epithelial-mesenchymal Transition Related Markers: In vitro and In vivo Studies.

Abstract

Background: Radioresistance is the primary cause of treatment failure in esophageal squamous cell carcinoma, emphasizing the importance of identifying effective radiosensitizers.

Objectives: This study aimed to explore the effects and potential mechanisms of Eg5 inhibitor K858 on the radiosensitivity of esophageal squamous cell carcinoma TE-1 and KYSE150 cell lines, as well as xenografts (TE-1 cells).

Methods: Cellular function was assessed using CCK8, wound healing, and transwell invasion assays. Radiosensitivity parameters were derived from colony formation assays. Cell apoptosis and cell cycle were assessed using flow cytometry, whereas protein expression levels were detected using western blotting and immunohistochemistry. The xenograft model was used to observe the growth of tumors.

Results: K858 inhibited the malignant functions of TE-1 and KYSE150 cell lines. Radiosensitivity parameters were reduced after K858 treatment. The combination of K858 and irradiation markedly suppressed cell proliferation, induced apoptosis, and stimulated cell cycle arrest during the irradiation-sensitive phase. Additionally, K858, combined with irradiation, significantly increased the expression of the epithelial-mesenchymal transition marker E-cadherin and decreased the expression of N-cadherin, vimentin, MMP2, and MMP9. K858, combined with irradiation, significantly inhibited tumor growth in xenograft models.

Conclusion: K858 enhanced the radiosensitivity of esophageal squamous cell carcinoma and affected the expression of epithelial-mesenchymal transition-related markers.