Objective: Cancer stem cells (CSCs) are responsible for cervical cancer progression and decreased radiosensitivity of tumor cells. The present work is meant to illuminate the impacts of exportin 1 (XPO1) on the aggressive behaviors and radiosensitivity of cervical cancer stemness cells and make a deeper inquiry into its regulatory mechanism despite that XPO1 has been supported to elicit significant activities on multiple malignancies.
Methods: XPO1 and Rad21 expression in HeLa (CD44+) cells was tested by RT-qPCR and western blot. Cell viability was estimated via CCK-8 assay. Cell stemness was examined via sphere formation assay and western blot. Following radiation treatment, cell proliferation was judged by CCK-8 assay, western blot as well as EdU staining whereas TUNEL assay, RT-qPCR and western blot analysis appraised cell apoptosis. Cell radiosensitivity was assessed through clonogenic survival assay. The levels of DNA damage markers were tested by western blot and related kits. STRING database and Co-IP assay respectively predicted and testified the binding of XPO1 with Rad21. RT-qPCR and western blot also examined the expression of XPO1 cargoes.
Results: The experimental data corroborated that XPO1 and Rad21 were overexpressed in cervical cancer tissues and cells. XPO1 inhibitor KPT-330 impeded the stemness while elevated the radiosensitivity of HeLa (CD44+) cells. XPO1 bond to Rad21 and positively modulated Rad21 expression. Moreover, Rad21 elevation reversed the impacts of KPT-330 on the behaviors of cervical cancer stemness cells.
Conclusion: To sum up, XPO1 might impact the aggressive behavior and radioresistance of cervical cancer stemness cells through binding with Rad21.
Keywords: Cervical cancer stemness cells; Rad21; XPO1; radiosensitivity.
© 2023 by the Association of Clinical Scientists, Inc.