Chondrosarcoma has a high propensity to metastasize and responds poorly to chemotherapy and radiation treatment. The enzymatic activity of matrix metalloproteinases (MMPs) is very important in chondrosarcoma metastasis. Melatonin exhibits anticarcinogenic activity in many types of cancers by suppressing the expression of certain MMP family members, but this has not yet been clearly determined in chondrosarcoma. Our study demonstrates that MMP7 plays an essential role in chondrosarcoma cell proliferation, migration, and anoikis resistance. We also found that MMP7 is highly expressed in chondrosarcomas. Our in vitro and in vivo investigations show that melatonin strongly inhibits chondrosarcoma cell proliferation, migration, and anoikis resistance by directly suppressing MMP7 expression. Melatonin reduced MMP7 synthesis by promoting levels of miR-520f-3p expression, which were downregulated in human chondrosarcoma tissue samples. Pharmacological inhibition of miR-520f-3p markedly reversed the effects of melatonin upon chondrosarcoma proliferation and metastasis. Thus, our study suggests that melatonin has therapeutic potential for reducing the tumorigenesis and metastatic potential of chondrosarcoma via the miR-520f-3p/MMP7 axis.

中文翻译：

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褪黑素通过增强 miR-520f-3p 的产生并抑制 MMP7 的表达来抑制软骨肉瘤细胞的增殖和转移

软骨肉瘤具有很高的转移倾向，并且对化疗和放射治疗的反应较差。基质金属蛋白酶（MMP）的酶活性在软骨肉瘤转移中非常重要。褪黑素通过抑制某些 MMP 家族成员的表达，在多种癌症中表现出抗癌活性，但在软骨肉瘤中这一点尚未明确确定。我们的研究表明，MMP7 在软骨肉瘤细胞增殖、迁移和失巢凋亡抵抗中发挥重要作用。我们还发现MMP7在软骨肉瘤中高表达。我们的体外和体内研究表明，褪黑激素通过直接抑制 MMP7 表达，强烈抑制软骨肉瘤细胞增殖、迁移和失巢凋亡抵抗。褪黑激素通过促进 miR-520f-3p 表达水平来减少 MMP7 合成，而 miR-520f-3p 表达水平在人软骨肉瘤组织样本中下调。miR-520f-3p 的药理学抑制显着逆转褪黑激素对软骨肉瘤增殖和转移的影响。因此，我们的研究表明褪黑激素具有通过 miR-520f-3p/MMP7 轴减少软骨肉瘤的肿瘤发生和转移潜力的治疗潜力。