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Application of melatonin in the preparation of medicaments for the treatment and adjuvant treatment of osteosarcoma

An adjuvant therapy, melatonin technology, applied in the direction of antineoplastic drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of poor tissue specificity, systemic toxic and side effects, and inability to accurately locate OS tissues

Active Publication Date: 2022-08-05
中国医科大学
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the existing chemotherapeutic drugs and antineoplastic drugs have the following shortcomings: poor tissue specificity, unable to accurately locate OS tissues, resulting in systemic toxic and side effects

Method used

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  • Application of melatonin in the preparation of medicaments for the treatment and adjuvant treatment of osteosarcoma
  • Application of melatonin in the preparation of medicaments for the treatment and adjuvant treatment of osteosarcoma
  • Application of melatonin in the preparation of medicaments for the treatment and adjuvant treatment of osteosarcoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Experimental process and results of the antitumor effect of melatonin on osteosarcoma cells

[0023] We used E-cadherin to label tumor cells, CD45 to label leukocytes, and CD68 to label macrophages, and fluorescently stained tumor tissue samples from 30 patients with osteosarcoma and observed CIC types (tumor cells engulfing tumor cells, tumor cells) using confocal laser microscopy. Leukocytes engulf leukocytes, and macrophages engulf tumor cells). We observed that the predominant type of CIC in the tumor tissue of patients with osteosarcoma was tumor cell phagocytosis of tumor cells, which could be observed in 26 of the 30 samples. However, leukocytes and macrophages mainly exist in the tumor microenvironment, and very few co-localize with tumor cells, only 3 and 5 cases were observed, respectively. These results suggest that CIC exists in the tumor tissue of patients with osteosarcoma, and its type is tumor cells engulfing tumor cells. The result is as f...

Embodiment 2

[0037] Example 2: Experimental process and results of the antitumor effect of melatonin composition on osteosarcoma cells

[0038] Example 1 image 3 The experimental results demonstrated that the combined application of inhibitors can reduce the metastatic ability of osteosarcoma cells. Therefore, the present invention further conducts experiments on the basis of Example 1, which proves that the combined use of melatonin and a ROCK inhibitor can enhance the efficacy of melatonin, and the ROCK inhibitor is preferably ROCK-IN-1 ( Chemical formula: C 20 H 18 FN 3 O, CAS No. 934387-35-6), the pairing ratio between it and melatonin is preferably between 1:3 and 3:1 by weight, most preferably 3:1. Other known ROCK inhibitors that inhibit ROCK2 activity can also be used.

[0039] We use the compound preparation of melatonin and ROCK inhibitor (ROCK-IN-1), which is administered at 10 mg / kg body weight (the weight ratio of melatonin and ROCK inhibitor is 1:1, 3:1, 1:3, respective...

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Abstract

The invention provides melatonin and the application of a melatonin composition in preparing a medicament for the treatment and auxiliary treatment of osteosarcoma. The present invention finds that the expression of melatonin receptor MT1 in osteosarcoma cells is increased through experimental research, and there is a phenomenon that the homogeneous CIC of tumor cells is increased. The application of melatonin can inhibit the key pathway of CIC Rho / ROCK, thereby inhibiting the same type of CIC, intervenes in the mitochondrial physiology of osteosarcoma cells, and plays an anti-invasive and metastatic role in osteosarcoma. Finally, the application of melatonin and a better melatonin composition in the preparation of medicines for the treatment and adjuvant treatment of osteosarcoma is provided, and new therapeutic targets and directions are provided for the clinic.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to the application of melatonin in the preparation of a medicament for the treatment and auxiliary treatment of osteosarcoma. Background technique [0002] Melatonin (MT) is a neuroendocrine hormone mainly secreted by the pineal gland, which has various physiological functions such as regulation of circadian rhythm, immune regulation, antioxidant and anti-inflammatory. In recent years, a large number of literatures have shown that MT has anti-tumor and chemopreventive effects, and the research on the anti-tumor effect of MT has become a hot spot, including the research on tumors such as breast cancer, melanoma, colon cancer and prostate cancer. Evidence suggests that multiple mechanisms are involved in the antitumor effects of MT, such as interfering with estrogen signaling and affecting telomerase activity. MT not only has a single anti-tumor effect, but also has syner...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4045A61K45/06A61P35/00
CPCA61K31/4045A61K45/06A61K2300/00
Inventor 张威林张治宇赵威
Owner 中国医科大学
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