2. Academic Validation
  3. The synergistic anticancer effect of CBD and DOX in osteosarcoma

The synergistic anticancer effect of CBD and DOX in osteosarcoma

  • Clin Transl Oncol. 2023 Feb 27. doi: 10.1007/s12094-023-03119-3.
Juncheng Li 1 2 3,  Wei Jiang 1 2 3,  Wenhao Shan 1,  Aiying Luo 1,  Gaoyang Qu 1 2 3,  Jiongfeng Zhang 1 2 3,  Xiaohui Luo 1 2 3,  Jian Xia 4 5 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi, China.
  • 2 Medical Department of Graduate School, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 3 The Key Laboratory of Tumor Metastasis and Precision Therapy of Jiangxi Province, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi, China.
  • 4 Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi, China. [email protected].
  • 5 Medical Department of Graduate School, Nanchang University, Nanchang, 330006, Jiangxi, China. [email protected].
  • 6 The Key Laboratory of Tumor Metastasis and Precision Therapy of Jiangxi Province, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi, China. [email protected].
PMID: 36848028 DOI: 10.1007/s12094-023-03119-3
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.

Keywords

Cannabidiol; Doxorubicin; MAPK; Osteosarcoma; PI3K/AKT/mTOR.

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