gms | German Medical Science

Background: Chondrosarcoma is a rare tumor entity, nevertheless accounting for 16-20% of all bone sarcomas. The most striking characteristic of chondrosarcoma is its's relatively high radio- and chemoresistance leaving surgery as the only curative treatment option. Considering that the survival rates for chondrosarcoma have stayed the same for the last decades there is a great demand for a curative systemic treatment. As found previously the anti-tumor effect of 2-Methoxyestradiol in chondrosarcoma cells can be enhanced via inhibition of autophagy. Metformin, a drug commonly used to treat type 2 Diabetes, is known to induce autophagy, whereas Hydroxychloroquine is known to be an inhibitor of autophagy. Considering the characteristics of these FDA-approved drugs their effect on chondrosarcoma cells should be investigated.

Objectives: This study aims to determine the effect of Metformin and Hydroxychloroquine on SW1353 chondrosarcoma cells. Furthermore we investigate the potential synergistic cytotoxic effect of Metformin and Hydroxychloroquine. Another aspect of this study is to determine the role of autophagy regarding the synergistic cytotoxic effect of this potential future treatment regimen.

Materials and Methods: In order to evaluate cell viability in SW1353 chondrosarcoma cells treated with Veh/Metformin +/- Hydroxychloroquine we use MTS-assays. We determine the time-dose-dependant cytotoxic properties of the treatment regimens mentioned above. Furthermore Western Blot analysis of LC3 I & II is used to determine the degree of induction/inhibition of autophagy via Metformin- and Hydroxychloroquine treatment. In order to investigate the influence of the treatment regimens on cell migration in vitro we perform in-vitro-scratch-assays.

Results: We evaluated the time-dose-dependant effects of Metformin and Hydroxychloroquine and determined 1mM and 20microgramg/ml respectively to be most suited for further experiments. We chose 1mM Metformin as a non-toxic concentration and 20microgram/ml Hydroxychloroquine as a slightly toxic concentration. The co-treatment of 1mM Metformin and Hydroxychloroquine was found to reduce cell viability to approximately 2%. Additionally we determined the degree of autophagy induction and the influence of the above mentioned treatment regimens on cell migration in vitro.

Conclusion: Concludingly our results suggest that autophagy might play a role in chemoresistance of chondrosarcoma. Furthermore our findings indicate that the Metformin-Hydroxychloroquine treatment regimen might be a new promising approach for finding a systemic treatment option for chondrosarcoma patients.