Abstract
BackgroundOsteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism.MethodsCCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects.ResultsNotably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway.ConclusionsIn brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.
Highlights
Osteosarcoma is the most common primary bone tumor in children and adolescents
It is very important to identify effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma
Cordycepin induces osteosarcoma cell apoptosis Above, we demonstrated that cordycepin can significantly inhibit the proliferation of osteosarcoma cells
Summary
Some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Standard adjuvant/ neoadjuvant chemotherapy does not have robust antineoplastic effects in some osteosarcoma patients [3, 4], and a considerable number of patients develop drug resistance to current chemotherapy regimens [5]. Many studies have shown that cordycepin has significant antitumor effects, promoting cell apoptosis and suppressing cell proliferation and invasion and tumor metastasis through various signaling pathways [9,10,11,12]. The inhibitory effect of cordycepin on osteosarcoma has not been reported, and the molecular mechanisms of its anti-tumor activity remain unclear
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