Pharmacodynamic Study of Brucea Javanica Oil on A549 Tumor Spheroids and HL60 Cells

• 1、School of Pharmaceutical Sciences, Medical College of Soochow University, Suzhou 215123

Abstract：Pharmacodynamic evaluation of anticancer drugs represents a critical focus in oncological research. Brucea Javanica Oil, a botanical extract from the Simaroubaceae family, demonstrates multifunctional antitumor mechanisms including apoptosis induction, suppression of drug-resistant enzymes, and immunomodulatory effects, with its clinical formulations utilized as adjuvant therapy for chemoradiation. However, tumor heterogeneity, immune evasion, and 3D tumor microenvironment characteristics may influence its pharmacodynamic responsiveness. This study constructed an A549 lung cancer spheroid model to simulate the 3D tumor microenvironment in vivo and employed HL60 immune cells to evaluate pharmacodynamic variations among Brucea Javanica Oil crude extract and three separated components. Results revealed that in the 3D spheroid system, the crude extract at 1×10^-4 concentration slightly enhanced A549 spheroid viability, while 1×10^-6 to 1×10^-5 concentrations exhibited no significant effects. At 1×10^-3 concentration, A549 spheroids displayed markedly higher viability, with the three separated components showing similar trends to the crude extract. These findings suggest that the 3D culture system, compared to traditional monolayer cultures, may attenuate drug efficacy due to altered tumor growth patterns. In HL60 immune cells, both the crude extract and separated components inhibited proliferation at 1×10^-3 concentration, whereas the crude extract exhibited pro-proliferative effects at 1×10^-6 concentration, with no significant changes observed for other components at lower concentrations, indicating concentration-dependent bidirectional regulatory properties of the oil on immune cells. The study demonstrates that 3D tumor microenvironments may diminish the anticancer efficacy of Brucea Javanica Oil, while its immunomodulatory effects are bidirectionally regulated by concentration gradients, providing experimental insights for optimizing clinical applications in anticancer therapy and combinatorial immunotherapy strategies.

Keywords： Traditional Chinese Medicine Brucea Javanica Oil A549 tumor spheroid HL60 cell Drug efficacy evaluation.