Kumar Ram Mohan Ram, Arlt Matthias Je, Kuzmanov Aleksandar, Born Walter, Fuchs Bruno
Department of Orthopaedics, Laboratory for Orthopaedic Research, Balgrist University Hospital, University of Zurich Zurich, Switzerland.
Am J Cancer Res. 2015 Jun 15;5(7):2156-68. eCollection 2015.
Osteosarcoma is a rare type of cancer that commonly occurs as a primary bone tumour in children and adolescents and is associated with a poor clinical outcome. Despite complex treatment protocols, including chemotherapy combined with surgical resection, the prognosis for patients with osteosarcoma and metastases remains poor and more effective therapies are required. In this study, we evaluated the therapeutic efficacy of sunitinib malate, a wide-spectrum tyrosine kinase inhibitor, in a preclinical mouse model of osteosarcoma. Sunitinib significantly inhibited proliferation, provoked apoptosis and induced G2/M cell cycle arrest in the human osteosarcoma cell lines SaOS-2 and 143B in vitro. Importantly, sunitinib treatment significantly reduced tumour burden, microvessel density and suppressed pulmonary metastasis in a 143B cell-derived intratibial osteosarcoma model in SCID mice. Sunitinib significantly decreased primary tumor tissue proliferation and reduced tumor vasculature. Our study indicates that sunitinib has potential for effective treatment of metastasizing osteosarcoma and provides the framework for future clinical trials with sunitinib alone or in combination with conventional and other novel therapeutics aiming at increased treatment efficacy and improved patient outcome.
骨肉瘤是一种罕见的癌症类型，通常作为儿童和青少年的原发性骨肿瘤出现，且临床预后较差。尽管有包括化疗联合手术切除在内的复杂治疗方案，但骨肉瘤伴转移患者的预后仍然很差，需要更有效的治疗方法。在本研究中，我们在骨肉瘤的临床前小鼠模型中评估了广谱酪氨酸激酶抑制剂苹果酸舒尼替尼的治疗效果。舒尼替尼在体外显著抑制人骨肉瘤细胞系SaOS-2和143B的增殖、引发凋亡并诱导G2/M期细胞周期阻滞。重要的是，在SCID小鼠的143B细胞源性胫骨内骨肉瘤模型中，舒尼替尼治疗显著降低了肿瘤负荷、微血管密度并抑制了肺转移。舒尼替尼显著降低了原发性肿瘤组织的增殖并减少了肿瘤血管。我们的研究表明，舒尼替尼具有有效治疗转移性骨肉瘤的潜力，并为未来单独使用舒尼替尼或与传统及其他新型疗法联合使用以提高治疗效果和改善患者预后的临床试验提供了框架。
