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Application of IFN-alpha and HDACi to preparation of medicine for treating tumor

A tumor drug and tumor technology, applied in the fields of biotechnology and medicine, can solve the problems of increased inflammatory signals, low immunogenicity, poor effect, etc., and achieve the effect of strengthening adjuvant therapy and improving the effect

Pending Publication Date: 2020-05-05
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] However, in the process of treating tumors with interferon, in general, the immunogenicity of tumor cells is not high, resulting in insignificant therapeutic effect of interferon. If the immunogenicity of tumor cells can be increased to a certain extent, the inflammation of tumor cells The signal increases, so that more immune cells will infiltrate into the tumor, enhancing the effect of tumor immunotherapy
Due to the specificity, stability and dose limitation of epigenetic drugs, the effect of these drugs on solid tumors has been poor

Method used

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  • Application of IFN-alpha and HDACi to preparation of medicine for treating tumor
  • Application of IFN-alpha and HDACi to preparation of medicine for treating tumor
  • Application of IFN-alpha and HDACi to preparation of medicine for treating tumor

Examples

Experimental program
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Effect test

Embodiment 1

[0035] Example 1 Screening for High Expression of HDAC3 in Liver Cancer Tissues

[0036] Select 6 pairs of primary liver cancer tissue samples (cancer and para-cancer) for Microarray mRNA expression profile analysis, cluster analysis of genes with significant differential expression, and focus on analysis of genes with high expression in the tumor and in the para-cancer according to the expression of differential genes. Clustering of genes with low expression, the results are shown in figure 1 . It was found that the expression of HDAC3 related to epigenetic regulation was significantly different in the tumor and adjacent tissues: the expression was high in the tumor, and the expression was low in the adjacent tissues. The results are shown in figure 2 .

Embodiment 2

[0037] Example 2 Verification of HDAC3 expression in tumor tissue samples from patients with liver cancer

[0038] From the mRNA microarray data of liver cancer tissues, it was found that the expression of HDAC3 was increased in tumor samples. Through the verification of the expression level of HDAC3 RNA in 12 pairs of liver cancer tissue samples, it was found that the expression of HDAC3 in tumor tissues was higher than that in adjacent tissues. The results are shown in image 3 . The above results indicated that the differential expression of HDAC3 in liver cancer was universal, and verified the results of the microarray.

Embodiment 3

[0039] Example 3 Cluster analysis of differentially expressed genes in liver cancer cells after IFN-α treatment

[0040] Based on the mRNA Microarray chip analysis of liver cancer tumor tissue, the liver cancer cell line HepG2 was treated with IFN-α for 6 hours and 24 hours respectively, and the genes differentially expressed in the chip before and after interferon treatment were detected. Through the cluster analysis of the "The Database for Annotation, Visualization and Integrated Discovery" (DAVID) database, it was found that the signaling pathways of genes whose expression was increased after IFN-α treatment for 6 hours were mainly enriched in genes related to antiviral infection and inflammation ( Figure 4 ), the signaling pathways of genes with reduced expression are mainly enriched in genes related to epigenetic regulation such as transcriptional regulation and DNA binding ( Figure 5 ). Among them, after interferon treatment, the expression level of HDAC3, which was ...

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Abstract

The invention discloses application of IFN-alpha and HDACi to preparation of a medicine for treating tumor, and belongs to the technical field of biotechnology and medical technology. Application of the IFN-alpha and HDACi disclosed by the invention to preparation of the medicine for treating tumor is disclosed. By using HDACi inhibitor, tumor cancers are treated, and then IFN-alpha is added, andverification shows that the inhibitor for epigenetic modification can further activate interferon-related signaling pathway STAT and expression of interferon responsive genes, recruits and activates parts, reaching the tumors, of immune cell subpopulations while inflammatory reaction of the inhibitor is enhanced, and the immunotherapy effect of the tumors is improved.

Description

technical field [0001] The invention relates to the fields of biotechnology and medical technology, and more specifically relates to the application of IFN-α and HDACi in the preparation of drugs for treating tumors. Background technique [0002] Tumor epigenetics refers to the general term for various abnormalities related to tumors that do not involve changes in nucleic acid sequences but can lead to changes in gene expression, mainly manifested in the reduction of DNA methylation levels in the entire genome and the loss of specific histone modifications 1. Hypermethylation inactivation of tumor suppressor gene promoter region and abnormal chromatin structure. All these epigenetic changes will affect the growth of tumor cells, immune escape, metastasis, heterogeneity and drug resistance, etc., and some may even directly lead to the occurrence of tumors. Since the characteristics of the genomic DNA sequence are not changed, these epigenetic abnormalities are reversible cha...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K38/21A61P35/00A61P1/16
CPCA61K38/212A61K45/06A61P1/16A61P35/00A61K2300/00
Inventor 曹雪涛李江雪王春梅
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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