Abstract

Resveratrol shows potent anti-tumor therapeutic properties in various tumors. However, the exact effect of resveratrol on osteosarcoma cells, especially cancer stem cells, remains unclear. In this study, we examined the effect of resveratrol on osteosarcoma stem cells and explored the underlying molecular mechanisms. Resveratrol inhibited cell viability, self-renewal ability and tumorigenesis of osteosarcoma cells, whereas showed no significant inhibition effects to normal osteoblast cells. Mechanically, resveratrol treatment decreased cytokines synthesis and inhibited JAK2/STAT3 signaling, which was consistent with the decline of cancer stem cells marker, CD133. Exogenous STAT3 activation attenuated the cancer stem cell elimination effects of resveratrol treatment. Our results demonstrated that resveratrol inhibited osteosarcoma cell proliferation and tumorigenesis ability, which was correlated with cytokines inhibition related JAK2/STAT3 signaling blockage. Resveratrol may be a promising therapeutic agent for osteosarcoma management.

Highlights

  • Osteosarcoma is the most common type of bone cancer and the second leading cause of cancer-related deaths in children and adolescents, which shows an incidence of 3.4 cases per million people every year worldwide. [1]

  • We examined the effect of resveratrol on osteosarcoma stem cells and explored the underlying molecular mechanisms of JAK2/STAT3 signaling pathway

  • Significant osteosarcoma stem cell elimination effects were observed with resveratrol treatment

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Summary

Introduction

Osteosarcoma is the most common type of bone cancer and the second leading cause of cancer-related deaths in children and adolescents, which shows an incidence of 3.4 cases per million people every year worldwide. [1]. Osteosarcoma is the most common type of bone cancer and the second leading cause of cancer-related deaths in children and adolescents, which shows an incidence of 3.4 cases per million people every year worldwide. Combination of surgery and adjacent chemotherapy is still the conventional therapeutic regimens for osteosarcoma patients [2]. Despite of the significant improvements in diagnosis and therapy over the last decades, about 60–70% osteosarcoma patients exhibit no benefit from these treatment [3]. The 5-year survival in patients with localized osteosarcoma is remained at 50% approximately, and only 15% for five-year survival estimation in the patients with lung metastasis [4]. Novel and effective agents are urgent needs for improving osteosarcoma therapeutic efficiency, especially natural compounds investigation

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