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The synergistic anticancer effect of CBD and DOX in osteosarcoma

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Abstract

Background

Osteosarcoma is a malignant tumor that can present with pain in the bones, joints, and local masses. The incidence is highest in adolescents, and the most common sites are the distal femur, proximal tibia and proximal humerus metaphyseal. Doxorubicin is the first-line chemotherapeutic agent for the treatment of osteosarcoma, but it has many side effects. Cannabidiol is a non-psychoactive plant cannabinoid cannabinol (CBD) that has been shown to be effective against osteosarcoma; however, the molecular targets and mechanisms of CBD action in osteosarcoma remain unclear.

Methods

Cell proliferation, migration, invasion and colony formation were analyzed using two drugs alone or in combination to evaluate their inhibitory effects on the malignant characteristics of OS cells. Apoptosis and the cell cycle were detected by flow cytometry. The synergistic inhibitory effect of doxorubicin/cannabidiol on tumors was also detected in nude mouse xenotransplantation models.

Results

Through analysis of two osteosarcoma cell lines, MG63 and U2R, it was found that the cannabidiol/doxorubicin combination treatment synergistically inhibited growth, migration and invasion and induced apoptosis, blocking G2 stagnation in OS cells. Further mechanistic exploration suggests that the PI3K-AKT-mTOR pathway and MAPK pathway play an important role in the synergistic inhibitory effect of the two drugs in osteosarcoma. Finally, in vivo experimental results showed that the cannabidiol/doxorubicin combination treatment significantly reduced the number of tumor xenografts compared to cannabidiol alone or doxorubicin alone.

Conclusions

Our findings in this study suggest that cannabidiol and doxorubicin have a synergistic anticancer effect on OS cells, and their combined application may be a promising treatment strategy for OS.

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Acknowledgements

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. This study was supported by grants from the Science and Technology Bureau of Jiangxi Province (20171BBG700153).

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Authors and Affiliations

Authors

Contributions

JX and JCL designed this research; JCL participated in conducting all the experiments; JCL and WJ performed western blotting and the drug treatment experiments; JCL, WJ and WHS performed the in vivo assay; JCL, JFZ, GYQ, XHL and AYL cultured osteosarcoma cell lines and assisted with data analysis; JCL and JX wrote the manuscript. All authors read and approved the fnal manuscript.

Corresponding author

Correspondence to Jian Xia.

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Conflict of interests

The authors declare that they have no competing interests.

Ethical approval

This study was approved by the institutional ethical review boards of the Third Affiliated Hospital of Nanchang University (Ethics approval number:MDL2022-10-01-15).

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Li, J., Jiang, W., Shan, W. et al. The synergistic anticancer effect of CBD and DOX in osteosarcoma. Clin Transl Oncol 25, 2408–2418 (2023). https://doi.org/10.1007/s12094-023-03119-3

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  • DOI: https://doi.org/10.1007/s12094-023-03119-3

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