阅读说明：本技术 Geiparvarin在制备抗骨肉瘤产品中的应用 (Application of Geiparvarin in preparation of anti-osteosarcoma product ) 是由 邹华 许成雄 黄萍 陈姝 王斌 肖何 张志敏 张亮 于 2019-12-05 设计创作，主要内容包括：本发明公开了Geiparvarin在制备治疗骨肉瘤产品中的应用,以及Geiparvarin在制备抑制骨肉瘤增殖产品中的应用。本发明首次发现Geiparvarin对多种骨肉瘤细胞的活力均有显著抑制作用,证实Geiparvarin能抑制HOS和143B骨肉瘤细胞的集落形成,促进细胞的凋亡,干预细胞周期,使细胞阻滞在G2期,并减少G1期细胞数量,细胞分裂能力受到抑制；并抑制HOS和143B骨肉瘤细胞的迁移。动物实验证实化合物Geiparvarin能明显抑制裸鼠皮下143B细胞瘤的体积,能较好的抑制骨肉瘤的生长。本发明发现了Geiparvarin用于骨肉瘤抗肿瘤治疗的新应用。(The invention discloses application of Geiparvarin in preparation of a product for treating osteosarcoma and application of Geiparvarin in preparation of a product for inhibiting osteosarcoma proliferation. The invention discovers that Geiparvarin has obvious inhibiting effect on the activity of various osteosarcoma cells for the first time, proves that Geiparvarin can inhibit the colony formation of HOS and 143B osteosarcoma cells, promotes the apoptosis of the cells, intervenes the cell cycle, makes the cells blocked in the G2 stage, reduces the number of the cells in the G1 stage and inhibits the cell division capability; and inhibit migration of HOS and 143B osteosarcoma cells. Animal experiments prove that the compound Geiparvarin can obviously inhibit the volume of subcutaneous 143B cell tumor of a nude mouse and can better inhibit the growth of osteosarcoma. The invention finds a new application of Geiparvarin in anti-tumor treatment of osteoma.)

Application of Geiparvarin in preparing products for treating osteosarcoma.

Application of Geiparvarin in preparation of products for inhibiting osteosarcoma proliferation.

3. Use according to claim 1 or 2, characterized in that: the product is a medicament or a kit.

Technical Field

The invention relates to the technical field of biological pharmacy, in particular to application of Geiparvarin in preparing an anti-osteosarcoma product.

Background

Osteosarcoma, which has an annual incidence of 1-3 persons/100 ten thousand persons, is a more common non-hematologic malignancy originating in mesenchymal tissue in adolescents or children. Osteosarcoma has a high risk of developing lung metastases and a poor prognosis. Currently, the treatment of osteosarcoma is mainly combined with surgery and systemic chemotherapy, and in the last fifty years, osteosarcoma chemotherapy is resistant to the combined application of four drugs, namely high-dose methotrexate, doxorubicin, cisplatin and ifosfamide. The treatment mode is basically unchanged since the 70 s of the 20 th century, and the treatment effect is hardly improved. The overall survival rate of osteosarcoma for 5 years is around 60%, with 14% of patients being insensitive to standard chemotherapy. There has been no breakthrough in the treatment of osteosarcoma to date. Therefore, the research and development of novel chemotherapeutic drugs with strong targeting and less toxic and side effects have great significance for treating osteosarcoma.

Natural drugs have contributed greatly to the discovery of modern drugs. Over one third of the new molecules approved by the U.S. Food and Drug Administration (FDA) in 1931 to 2013 were derived or inspired from natural products. The proportion of natural drugs among the approved anticancer drugs over the last five years is even higher, half of these drugs being natural. The research of natural products provides continuous lead compounds for the discovery of new antitumor drugs, and the probability of discovering new antitumor drugs from natural products is far greater than that of synthetic compounds.

Geiparvarin is a natural compound extracted from Geijera parviflora of Australia, has a structure discovered and reported by Lahey F in 1967, and has a molecular formula of C₁₉H₁₈O₅Molecular weight 326.34, and has the following structure:

disclosure of Invention

The invention aims to solve the problems and provides an application of Geiparvarin in preparing an anti-osteosarcoma product.

In order to achieve the purpose, the invention adopts the technical scheme that:

provides the application of Geiparvarin in preparing products for treating osteosarcoma.

Provides the application of Geiparvarin in preparing products for inhibiting osteosarcoma proliferation.

The product is a medicament or a kit.

Geiparvarin is a natural compound, and can be administered in the form of injection or infusion solution without oral administration.

The invention has the beneficial effects that: geiparvarin is found to have a remarkable inhibiting effect on the activity of various osteosarcoma cells for the first time, and further activity-oriented component research finds that the Geiparvarin possibly has 3(2H) -furanone key fragments so as to show antitumor activity. The research of the invention proves that Geiparvarin can inhibit the colony formation of HOS and 143B osteosarcoma cells, promote the apoptosis of HOS and 143B cells, intervene in the cycle of HOS and 143B cells, block the cells in the G2 stage, reduce the number of cells in the G1 stage and inhibit the cell division capability; and inhibit migration of HOS and 143B osteosarcoma cells. Animal experiments prove that the compound Geiparvarin can obviously inhibit the volume of subcutaneous 143B cell tumor of a nude mouse and can better inhibit the growth of osteosarcoma. The invention finds a new application of Geiparvarin in anti-tumor treatment of the osteoma, and provides a new product for anti-tumor treatment of the osteoma.

Drawings

FIG. 1 shows the results of cell activity 48h after treating osteosarcoma cells with Geiparvarin at different concentrations.

FIG. 2 shows the result of observing the inhibition effect of Geiparvarin on cell colony formation 12 days after treating osteosarcoma cells with Geiparvarin at the same concentration.

FIG. 3 shows the survival rate of osteosarcoma cells after co-culture of different concentrations of Geiparvarin and HOS cells.

FIG. 4 is a graph of the results of flow assays of the effect of Geiparvarin on the HOS cell cycle.

FIG. 5 is a graph of the statistical results of the effect of Geiparvarin on the HOS cell cycle.

FIG. 6 is a graph of the results of flow assays of the effect of Geiparvarin on the 143B cell cycle.

Figure 7 is a graph of statistics of the effect of Geiparvarin on the 143B cell cycle.

FIG. 8 is a graph showing the results of flow-based assays of the effect of Geiparvarin on apoptosis in 143B and HOS cells.

FIG. 9 is a graph of statistics of Geiparvarin effect on apoptosis in 143B and HOS cells.

FIG. 10 is the effect of Geiparvarin on 143B and HOS cell migration.

FIG. 11 is a graph of the effect of Geiparvarin on tumor volume in 143B cell nude mice subcutaneously implanted tumors.

Detailed Description

The invention is further illustrated by the following examples, which are not intended to be limiting.

The experimental procedures in the following examples are conventional unless otherwise specified.

The sources of reagents used in the examples of the invention are as follows:

osteosarcoma HOS, Saos-2, 9901, MG-63, 9607, SW1353, U2OS cell lines were purchased from ATCC (American type culture Collection);

osteosarcoma 143B cell line was purchased from cell resource center of Shanghai Biopsis, Chinese academy of sciences;

geiparvarin has a CAS number of 36413-91-9, and examples of the present invention are available from Unigen, inc.

The mice are purchased from the experimental animal center of China civil liberation army military medical university;

DMEM media was purchased from BI corporation;

the cell cycle and apoptosis detection kit is purchased from Biyuntian biotechnology limited company.