2. Academic Validation
  3. Synergistic anticancer effects of SMYD2 inhibitor BAY-598 and doxorubicin in non-small cell lung cancer

Synergistic anticancer effects of SMYD2 inhibitor BAY-598 and doxorubicin in non-small cell lung cancer

  • Heliyon. 2024 May 29;10(11):e32015. doi: 10.1016/j.heliyon.2024.e32015.
Jiaqi Meng 1 2,  Weichang Yang 2 3,  Can Li 1,  Fengyuan Li 1 2
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi, China.
  • 2 Medical Department of Graduate School, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 3 Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
PMID: 38947456 DOI: 10.1016/j.heliyon.2024.e32015
Abstract

Background: Non-small cell lung Cancer (NSCLC) persists as a lethal neoplastic manifestation, exhibiting a diminished 5-year survival rate, partially attributable to chemotherapeutic resistance. This investigative endeavor aimed to elucidate the synergistic antineoplastic effects and underlying mechanisms of the SMYD2 Inhibitor BAY-598 and the chemotherapeutic agent doxorubicin (DOX) in NSCLC.

Methods: The human non-small cell lung Cancer cell lines A549 and H460 were subjected to treatment regimens involving BAY-598 and/or DOX. Cellular viability, apoptotic events, invasive capacity, and migratory potential were evaluated through the implementation of CCK-8 assays, flow cytometric analyses, and Transwell assays, respectively. Protein expression levels were quantified via Western blot analyses. An in vivo xenograft murine model was established to assess therapeutic efficacy.

Results: BAY-598 and DOX synergistically suppressed the viability, invasiveness, and migratory capabilities of NSCLC cells. Co-treatment Promoting cell Apoptosis and cell cycle arrest. Additionally, Furthermore, co-administration significantly inhibited cell migration and invasion. Mechanistic studies revealed coordinately inhibited JAK-STAT signaling upon combination treatment. In vivo study further validated the synergistic antitumor efficacy of BAY-598 and DOX against NSCLC xenografts.

Conclusions: Our findings demonstrate that BAY-598 potentiates the anti-cancer effects of DOX in non-small cell lung Cancer cells by modulating the JAK/STAT signaling pathway as a synergistic strategy. The combination holds promise as an emerging therapeutic strategy for NSCLC. Further optimization and validation are warranted to promote its translational potential.

Keywords

BAY-598; DOX; JAK/STAT signaling; NSCLC.

Figures
Products