Amplifying Antitumor Efficacy: The Role of UDCA in Modulating Autophagy and Enhancing DOX Response in NSCLC

Abstract

Abstract Background Non-small cell lung cancer (NSCLC) has long been challenged by the complexities of chemotherapeutic resistance, with autophagy playing a pivotal role in this resistance matrix. The multifaceted interplay between autophagy and tumor behavior, particularly in the context of NSCLC, demands nuanced understanding, given its contradictory roles in tumorigenesis and tumor survival. Methods We embarked on an intricate exploration of UDCA's potential in modulating the MAPK pathway, which is instigated by DOX. A systematic evaluation was undertaken of its influence on key autophagy-associated proteins and the cascading effects on pivotal signaling pathways, accentuating the role of TGFβ in this network. Results Our data illuminated that UDCA exerts a discernible inhibitory effect on tumor cell proliferation and alters the MAPK dynamics intricately associated with key proteins. Notably, the combined might of UDCA and DOX demonstrated a significant downregulation of TGFβ expression, thereby achieving a pronounced retardation in tumor progression without amplifying associated toxicities. Yet, exogenously introduced TGF-β presented a mitigating counter-effect. Conclusions Our findings advocate for UDCA's prospective utility as a potent chemosensitizer, amplifying the therapeutic efficacy of DOX against NSCLC by tactically inhibiting autophagy. This underscores the imperative for further exploration, moving us closer to tailoring precision-based therapeutic regimens centered on UDCA’s unique autophagy modulation capabilities.