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Application of melatonin in preparation of medicine for treating and adjunctively treating osteosarcoma

An adjuvant therapy, melatonin technology, applied in anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as inability to accurately locate OS tissue, poor tissue specificity, and systemic side effects

Active Publication Date: 2020-06-16
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 preparation of medicine for treating and adjunctively treating osteosarcoma
  • Application of melatonin in preparation of medicine for treating and adjunctively treating osteosarcoma
  • Application of melatonin in preparation of medicine for treating and adjunctively treating osteosarcoma

Examples

Experimental program
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Effect test

Embodiment 1

[0022] Example 1: Experimental process and results of melatonin's tumor inhibitory effect on osteosarcoma cells

[0023] We used E-cadherin to mark tumor cells, CD45 to mark leukocytes, and CD68 to mark macrophages. We performed fluorescent staining on tumor tissue samples of 30 patients with osteosarcoma and observed the CIC types in the samples (tumor cells engulfed tumor cells, tumor cells engulf leukocytes, macrophages engulf tumor cells). We observed that the main type of CIC in the tumor tissue of patients with osteosarcoma was tumor cell phagocytosis, and 26 cases were observed in 30 samples. While leukocytes and macrophages mainly existed in the tumor microenvironment, very few co-localized with tumor cells, and only 3 and 5 cases were observed respectively. These results indicated that CIC existed in the tumor tissues of patients with osteosarcoma, and its type was tumor cell phagocytosis. The result is as figure 1 Shown are the results of immunofluorescence, where...

Embodiment 2

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

[0038] Example 1 image 3 The experimental results proved that 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, and proves that the combined use of melatonin and ROCK inhibitors 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 matching ratio between it and melatonin is preferably between 1:3 and 3:1 by weight, most preferably 3:1. Other ROCK inhibitors known to inhibit ROCK2 activity may also be used.

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

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Abstract

The invention provides melatonin and application of a melatonin composition in preparation of a medicine for treating and adjunctively treating osteosarcoma. It is found in experimental research thatthe expression of melatonin receptor MT1 in osteosarcoma cells is increased, and tumor cell homogeneous CIC increasing is observed, using of melatonin can inhibit the CIC key pathway Rho / ROCK throughthe cAMP / PKA signal pathway, so that the homogeneous CIC can be inhibited, the mitochondrial physiology of osteosarcoma cells can be intervened, and the anti-osteosarcoma invasion and anti-metastasiseffects can be provided. Finally, application of melatonin and a better melatonin composition in preparation of medicine for treatment and adjuvant therapy of osteosarcoma is provided, and new treatment targets and directions are provided for 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 medicines for treating and adjuvantly treating osteosarcoma. Background technique [0002] Melatonin (MT) is a neuroendocrine hormone mainly secreted by the pineal gland, which has many physiological functions such as regulating circadian rhythm, immune regulation, anti-oxidation and anti-inflammation. In recent years, a large number of documents have shown that MT has anti-tumor and chemopreventive effects. The research on the anti-tumor effect of MT has become a hot spot, including studies on breast cancer, melanoma, colon cancer and prostate cancer. Evidence indicates 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 an independent tumor-suppressing effect, but also has synergistic and toxic-reducing ...

Claims

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Application Information

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Patent Type & Authority Applications(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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