Application of bleomycin in inhibition of PD-L1 high-expression tumors

A technology of PD-L1 and boningmycin, which is applied in the direction of antineoplastic drugs, medical preparations containing active ingredients, organic active ingredients, etc., can solve the problem of limiting the clinical application of immune checkpoint inhibitors and the low overall response rate of patients problems, to achieve the effect of improving the treatment effect, reducing the treatment cost and improving the treatment effect

Pending Publication Date: 2021-03-12
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although PD-L1 antibody therapy has obvious advantages, the overall response rate of patients is not high, about 20%-40%, which limits the clinical application of immune checkpoint inhibitors

Method used

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  • Application of bleomycin in inhibition of PD-L1 high-expression tumors
  • Application of bleomycin in inhibition of PD-L1 high-expression tumors
  • Application of bleomycin in inhibition of PD-L1 high-expression tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1. Inhibitory effect of boningmycin on the proliferation of human lung cancer NCI-H460 cells

[0019] 1.1. Experimental materials

[0020] The purity of boningmycin (BON) is greater than 95% (the relevant HPLC identification method is the same as the patent CN101607986A, a method for chemical semi-synthetic preparation of boningmycin);

[0021] NCI-H460 cells were purchased from the Cell Center of the Institute of Basic Medicine, Chinese Academy of Medical Sciences;

[0022] RPMI-1640 medium (C11875500BT), fetal bovine serum (FBS, 10099-141), Hank's balanced salt buffer (Hank's balanced salt solution, HBSS, 14025-092) and 0.25% trypsin (Trypsin-EDTA) , 25200-072) were purchased from Thermo Fisher Scientific Co., Ltd. (Gibco);

[0023] 60mm plate (430166) and 96-well plate (3599) for culturing cells were purchased from Corning Company;

[0024] CCK-8 reagent (B34302) was purchased from Bimake Company.

[0025] 1.2. Experimental method

[0026] (1) After the ...

Embodiment 2

[0034] Example 2: Boninomycin or bleomycin specifically reduces PD-L1 protein level in NCI-H460 cells in a short time

[0035] 2.1. Experimental materials

[0036] PD-L1 antibody (#13684, 1:1000) was purchased from Cell Signaling Technology;

[0037] β-actin antibody (sc-47778, 1:100000) was purchased from Santa Cruz Biotechnology;

[0038] Horseradish peroxidase-labeled goat anti-rabbit (1:1000 dilution, HS101-01) and goat anti-mouse (1:1000, HS201-01) secondary antibodies were purchased from Beijing Quanzhou Gold Biotechnology Co., Ltd;

[0039] Sodium dodecyl sulfonate was purchased from Sigma-Aldrich;

[0040] 40% (W / V) acrylamide (Invitrogen, HC2040) was purchased from Thermo Fisher Scientific Co., Ltd.;

[0041] Bradford Protein Assay Solution (#500-0205), ECL plus Chemiluminescence Color Solution (#170-5661), Pre-stained Marker (#161-0374), Tetramethylethylenediamine (TEMED, #161-0801), Thick filter paper and 3mm thin filter paper are from Bio-Rad Company;

[0042...

Embodiment 3

[0059] Example 3: Boningmycin significantly reduces the level of inducible PD-L1 protein in A549 cells

[0060] The expression level of PD-L1 protein in human lung cancer A549 cells was at a low level, and after treatment with recombinant human interferon IFN-γ, the level of PD-L1 protein increased significantly. If the treatment with boningmycin can significantly reduce the protein level of PD-L1, it shows that its effect is specific. The detection method adopted in this example is the same as that in Example 2, which is also Western blot.

[0061] 3.1. Experimental materials

[0062] Human non-small cell lung cancer A549 cells were purchased from the Cell Center of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences;

[0063] Recombinant human IFN-γ (#300-02) was purchased from Peprotech;

[0064] F12 medium (C11765500BT) was purchased from Thermo Fisher Scientific Co., Ltd. (Gibco).

[0065] 3.2. Experimental method

[0066] 3.2.1. Cell culture...

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Abstract

The invention relates to application of bleomycin in inhibition of PD-L1 high-expression tumors. The PD-L1 high-expression tumors are PD-L1 receptor natural high-expression tumors or PD-L1 receptor high-expression tumors caused by tumor treatment. The invention further relates to application of bleomycin or the pharmaceutically acceptable salt thereof in preparation of a combined preparation for treating tumors.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and in particular relates to an application of boningmycin for inhibiting tumors with high PD-L1 expression. Background technique [0002] Boningmycin is a new antibiotic with a single chemical structure obtained by fermentation and isolated from the soil of Pingyang City, Zhejiang Province by the Institute of Medical Biotechnology, Chinese Academy of Medical Sciences. Mycin family (patent number: 98101253.1, name of invention: an anti-tumor antibiotic and its microbial fermentation production method). Boninomycin can inhibit the proliferation of tumor cells and the growth of tumors in nude mice, such as human liver cancer and esophageal cancer, and has good antitumor activity. In addition, boningomycin has a strong inhibitory effect on psoriasis and seborrheic dermatitis (patent number: 03141374, invention name: new use of boningomycin in the treatment of psoriasis and seborrheic der...

Claims

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Application Information

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IPC IPC(8): A61K38/14A61K45/06A61K31/5377A61P35/00
CPCA61K38/14A61K45/06A61K31/5377A61P35/00
Inventor 何琪杨张娟解云英陈阳陈汝贤许鸿章
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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