Inhibition of Kpnβ1 mediated nuclear import enhances cisplatin chemosensitivity in cervical cancer

Abstract Background Inhibition of nuclear import via Karyopherin beta 1 (Kpnβ1) shows potential as an anti-cancer approach. This study investigated the use inhibitor, INI-43, in combination with cisplatin. Methods Cervical cancer cells were pre-treated INI-43 before treatment cisplatin, and MTT cell viability apoptosis assays performed. Activity localisation p53 NFκB was determined after co-treatment cells. Results Pre-treatment cervical at sublethal concentrations enhanced cisplatin sensitivity, evident through decreased apoptosis. Kpnβ1 knock-down similarly displayed increased sensitivity to Combination index determination using Chou-Talalay method revealed that engaged synergistic interactions. found be involved death response its inhibition abolished observed. pre-treatment resulted moderately stabilized induced reporter activity, which translated p21 Mcl-1 upon treatment. Furthermore, led NFκB, diminished INI-43. activity expression transcriptional targets, cyclin D1, c-Myc XIAP, showed levels compared single this associated DNA damage. Conclusions Taken together, significantly enhances cells, mediated stabilization NFκB. Hence suggests possible treat cancer.