Lobaplatin Enhances Radioactive I Seed-Induced Apoptosis and Anti-Proliferative Effect in Non-Small Cell Lung Cancer by Suppressing the AKT/mTOR Pathway

Introduction: In recent years, radioactive I seed implantation combined with chemotherapy has been regarded as a safe and effective treatment for advanced non-small cell lung cancer (NSCLC). However, the mechanism underlying this success is still unclear.

Methods: In this study, we investigated the apoptosis and anti-proliferative effect induced by I in A549, H1975, and H157 cells and determined whether a sensitizing concentration of lobaplatin (LBP) could enhance these effects. We performed in vitro experiments on A549, H1975, and H157 cells; we investigated the effects of I or lobaplatin (LBP) alone, or in combination, on cellular apoptosis and proliferation by performing flow cytometry, Bax/Bcl2 ratio, TUNEL, cell viability assay, cell cycle, and EdU. To further verify our findings, a subcutaneous tumor mouse model was established. Moreover, AKT/mTOR pathway was detected to determine whether this pathway was involved in the anti-cancer effect of I and LBP by up-regulating or down-regulating the expression of mTOR.

Results: Based on our results, the sensitizing concentration of LBP could enhance the I-induced apoptosis and anti-proliferation effect. Furthermore, the subcutaneous tumor mouse model obtained the consistent results. More importantly, the AKT/mTOR pathway was down-regulated after the treatment of I and LBP, and the anti-cancer effect of I and LBP could be compromised by up-regulating the mTOR expression.

Conclusion: Our study proved that LBP promotes the apoptotic and anti-proliferative effects of I in NSCLC cells by inhibiting the AKT/mTOR pathway and provides a foundation for future studies and enhanced combinatorial approaches for NSCLC in the clinical setting.