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褪黑素通过抑制整合素 αβ 表达抑制成骨前列腺癌的转移潜能。

Melatonin suppresses the metastatic potential of osteoblastic prostate cancers by inhibiting integrin α β expression.

机构信息

School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.

Department of Urology, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan.

出版信息

J Pineal Res. 2022 Apr;72(3):e12793. doi: 10.1111/jpi.12793. Epub 2022 Mar 10.

Abstract

Advanced prostate cancer often develops into bone metastasis, which is characterized by aberrant bone formation with chronic pain and lower chances of survival. No treatment exists as yet for osteoblastic bone metastasis in prostate cancer. The indolamine melatonin (N-acetyl-5-methoxytryptamine) is a major regulator of the circadian rhythm. Melatonin has shown antiproliferative and antimetastatic activities but has not yet been shown to be active in osteoblastic bone lesions of prostate cancer. Our study investigations reveal that melatonin concentration-dependently decreases the migratory and invasive abilities of two osteoblastic prostate cancer cell lines by inhibiting FAK, c-Src, and NF-κB transcriptional activity via the melatonin MT receptor, which effectively inhibits integrin α β expression. Melatonin therapy appears to offer therapeutic possibilities for reducing osteoblastic bone lesions in prostate cancer.

摘要

晚期前列腺癌常发展为骨转移,其特征为异常骨形成伴慢性疼痛和生存机会降低。目前尚无针对前列腺癌成骨性骨转移的治疗方法。吲哚胺褪黑素(N-乙酰-5-甲氧基色胺)是昼夜节律的主要调节剂。褪黑素具有抗增殖和抗转移活性,但尚未显示对前列腺癌成骨性骨病变有活性。我们的研究表明,褪黑素通过褪黑素 MT 受体浓度依赖性地抑制黏着斑激酶(FAK)、c-Src 和 NF-κB 转录活性,从而有效抑制整合素αβ表达,降低两种成骨性前列腺癌细胞系的迁移和侵袭能力。褪黑素治疗似乎为减少前列腺癌的成骨性骨病变提供了治疗可能性。

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