EIF5A2 Promotes Doxorubicin Resistance in Bladder Cancer Cells through the TGF-β Signaling Pathway

Background: Doxorubicin (DOX) is a commonly used chemotherapeutic agent, but bladder cancer (BC) patients often develop resistance that limits therapeutic efficacy. Recent research has demonstrated a link between medication resistance and the expression of eukaryotic translation initiation factor 5A2 (EIF5A2) in tumors. This study aimed to investigate whether EIF5A2 affects the resistance of BC cells to doxorubicin through the transforming growth factor (TGF)-β signaling pathway. Methods: Doxorubicin-resistant cells in BC (T24/DOX and 5637/DOX) were constructed, then cell viability was detected by cell counting kit-8 (CCK-8); EIF5A2 mRNA expression was detected using quantitative real-time PCR (qRT-PCR); cell proliferation was detected using clone formation; apoptosis was detected by flow cytometry; and finally, proteins related to the TGF-β signaling pathway (EIF5A2, TGF-β1, p-small mothers against decapentaplegic 2 (Smad2)/Smad2, p-Smad3/Smad3) were detected using western blot. Results: EIF5A2 was up-regulated in DOX-resistant BC cells, and DOX intervention promoted proliferation and inhibited apoptosis in DOX-resistant BC cells. si-EIF5A2 reversed the above effects. EIF5A2 resulted in DOX resistance by activating the TGF-β pathway, and the TGF-β activator SRI-011381 reversed the inhibitory effect of si-EIF5A2 on DOX resistance. Conclusions: EIF5A2 promotes DOX resistance in BC cells through the TGF-β signaling pathway, and EIF5A2 may be a potential counter-resistance therapeutic strategy in BC chemotherapy.