Anesthetic-chemotherapy interplay in osteosarcoma: preliminary investigations with in vitro models.

BACKGROUND

The primary objective of this study is to evaluate whether anesthetic agents modulate the apoptotic activity and migration-inhibitory effects of chemotherapeutic agents, thereby informing the optimization of perioperative management strategies in oncologic interventions.

METHODS

SAOS-2 cells were treated with varying concentrations of thiopental, ketamine, and doxorubicin. Cell viability was assessed via MTT assay to determine IC₅₀ values. Thiopental exhibited greater antiproliferative activity than ketamine and was selected for further study. Its interaction with doxorubicin was analyzed using the Chou-Talalay method, yielding a combination index (CI) of 0.92608 at Fa = 0.5, indicating moderate synergism. The combination treatment also led to reduced IC₅₀ values. Cell migration was evaluated using a scratch wound healing assay. Gene expression changes related to apoptosis and metastasis were analyzed using qRT-PCR. In silico molecular docking simulations were performed to provide mechanistic insights into the observed biological effects.

RESULTS

Thiopental and doxorubicin exhibited dose-dependent cytotoxicity, with the combination showing enhanced antiproliferative activity. Co-treatment reduced IC₅₀ values and suppressed SAOS-2 cell migration more effectively than either drug alone. Gene expression analysis revealed increased pro-apoptotic markers and decreased Bcl-2 expression. Metastasis-associated genes were significantly downregulated, despite upregulation of hypoxia-responsive genes. Molecular docking analyses identified interactions of thiopental and doxorubicin with HSP70, HSP90, and CYP450, providing complementary information for the interpretation of the observed cellular responses.

CONCLUSION

The findings suggest that thiopental may influence the cellular response to doxorubicin in osteosarcoma through treatment-associated modulation of apoptosis- and migration-related molecular responses. The observed moderate synergistic interaction and dose-reduction potential warrant further investigation in more clinically relevant experimental models.