Apatinib and Adebrelimab Exhibit Synergistic Antitumor effects in Small Cell Lung Cancer: An In Vitro Study.

Abstract

Background: Small cell lung cancer (SCLC) is a highly aggressive malignancy. This study investigated whether Apatinib (Apa) combined with Adebrelimab (Ade) exerted synergistic effects against SCLC.

Methods: Half-maximal inhibitory concentration (IC50) value of Apa and Ade, administered alone or in combination, was determined in H446 and H1436 cells using cell counting kit-8 (CCK-8) assays. Synergistic effects were quantified by calculating fractional inhibitory concentration (FIC) indices. Cell proliferation, migration, and invasion were assessed by CCK-8, wound healing, and Transwell assays, respectively. After co-culture with CD8+ T cells, PD-L1 expression and CD8+ IFN-γ+ T cell proportion were measured by flow cytometry. TGF-β secretion and LDH release were detected using ELISA and LDH assay, respectively; the protein level of VEGFR2 and STAT3 was analyzed by western blot.

Results: Apa alone exhibited IC50 values of 20.03 μM (H446) and 35.50 μM (H1436), while Ade alone exhibited 5.789 μM and 6.959 μM, respectively. The sum FIC values were 0.681 for H446 cells and 0.973 for H1436 cells. Compared with either monotherapy, combined treatment more effectively reduced cell viability, migration, and invasion. In co-culture experiments, the combination further suppressed PD-L1 expression and TGF-β secretion, increased CD8+ IFN-γ+ T cells and LDH release, and downregulated VEGFR2, p-STAT3, and PD-L1 protein levels.

Discussion: This study demonstrated that the combination of Apa and Ade exerted synergistic anti-tumor effects against SCLC in vitro. Further investigation, including animal studies and clinical trials, is warranted to evaluate the efficacy and long-term safety of this combination therapy.

Conclusion: In summary, the combination of Apa and Ade represented a promising innovative therapeutic strategy for SCLC.