Abstract
Melatonin (Mlt) confers potential antitumor effects in various types of cancer. However, to the best of our knowledge, the role of Mlt in the giant cell tumor of bone (GCTB) remains unknown. Moreover, further research is required to assess whether Mlt can enhance the therapeutic effect of zoledronic acid (Zol), a commonly used anti-GCTB drug. In this research, we investigated the effects of Mlt, Zol, and the combination of these two drugs on GCTB cells’ characteristics, including cell proliferation, apoptosis, osteogenic differentiation, migration, and invasion. The cell counting kit-8 (CCK-8) assay, colony formation assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL), alkaline phosphatase (ALP) staining, alizarin red staining (ARS), scratch wound healing assay, and transwell experiment were performed, respectively. Our results showed that Mlt could effectively inhibit the proliferation, migration, and invasion of GCTB cells, as well as promote the apoptosis and osteogenic differentiation of tumor cells. Of note, a stronger antitumor effect was observed when Mlt was combined with Zol treatment. This therapeutic effect might be achieved by inhibiting the activation of both the Hippo and NF-κB pathways. In conclusion, our study suggests that Mlt can be a new treatment for GCTB, which could further enhance the antitumor effect of Zol.
Highlights
Giant cell tumor of bone (GCTB) is a benign but aggressive bone tumor, which has the potential to destroy the bone and invade into the surrounding soft tissue
We found that different concentrations of Mlt or zoledronic acid (Zol) inhibited the proliferation of giant cell tumor of bone (GCTB) cells, and the effects of high concentrations were more obvious (Figures 1A,B)
Via the mRNA detection of proliferation markers CYCLIN B1, PCNA, and KI67, we found that treatment with different concentrations of Mlt and Zol suppressed the mRNA expression of proliferation markers (Figures 1G,H), and the mRNA and protein detection of proliferation markers showed that the combination of the two drugs showed a stronger inhibitory effect (Figures 1I,J)
Summary
Giant cell tumor of bone (GCTB) is a benign but aggressive bone tumor, which has the potential to destroy the bone and invade into the surrounding soft tissue. This leads to local pain and metastasis (Szendroi, 2004; Alberghini et al, 2010; Verschoor et al, 2018). Surgical resection is the primary treatment for GCTB; this treatment is not applicable in some sections of the body, such as the skull, pelvis, and spine. 15–50% patients still experience local tumor recurrence after surgical treatment F. et al, 2013; van der Heijden et al, 2014).
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