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Application of DC661 in treatment of hepatocellular carcinoma

A technology for hepatocellular carcinoma and its use, which is applied in the field of prevention and/or treatment of hepatocellular carcinoma, and can solve the problems of high risk of patients and impact on treatment effect, etc.

Inactive Publication Date: 2021-08-03
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The purpose of the present invention is to provide the application of DC661 in the treatment of hepatocellular carcinoma, to solve the problem that the surgical treatment of hepatocellular carcinoma in the prior art will inevitably bring higher risks to patients, and the use of molecular targeted drugs for treatment due to adaptive resistance The occurrence of drugs and serious side effects affect the treatment effect

Method used

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  • Application of DC661 in treatment of hepatocellular carcinoma
  • Application of DC661 in treatment of hepatocellular carcinoma
  • Application of DC661 in treatment of hepatocellular carcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1. DC661 inhibits the activity of human hepatocellular carcinoma cell line Hep 3B cells

[0029] The human hepatocellular carcinoma cell line Hep 3B cells as in Example 1 above were used as an in vitro experimental model, and the human hepatic carcinoma cell line Hep 3B cells were divided into two groups, namely the control group (treated with PBS) and the DC661 group. Different concentrations of DC661 (DC661 purchased from TargetMol, catalog number: T5538) were used to treat the human hepatocellular carcinoma cell line Hep 3B for IC50 test, CCK8 assay, Western blot and lysosomal LT green fluorescent probe staining analysis.

[0030] cck8 cell viability detection, DC661 has a dose-dependent anti-tumor effect ( figure 1 B), showing that DC661 inhibits the activity of human hepatocellular carcinoma cells. IC50 results as figure 1 C shown. After DC661 (3μM, 6h) treatment, the staining of the lysosomal LT green fluorescent probe was weakened, and the fluorescent ...

Embodiment 2

[0031]Example 2, DC661 inhibits the expression of genes and proteins that maintain lysosomal membrane stability in human hepatocellular carcinoma cells

[0032] The human hepatocellular carcinoma cell line Hep 3B cells as in Example 1 above were used as an in vitro experimental model, and the human hepatic carcinoma cell line Hep 3B cells were divided into two groups, namely the control group (treated with PBS) and the DC661 group. The human hepatocellular carcinoma cell line Hep 3B cells were treated with 3 μM DC661, and the key gene HSP70.1 and its transcription factor HSF1, which maintain the stability of the lysosomal membrane, were detected at 6 hours.

[0033] The results of Western blot showed that compared with the control group, DC661 significantly down-regulated the expression of HSP70.1 protein (*p figure 2 A and 2B). Protein expression was verified in another way by treating HSP70.1 on Hep 3B cells with the above conditions for immunofluorescence staining. The res...

Embodiment 3

[0034] Example 3, DC661 induces apoptosis of human hepatocellular carcinoma cells

[0035] Human hepatocellular carcinoma cell line Hep 3B cells were treated with 3 μM DC661, and immunofluorescent staining was performed at 6 hours to detect the intracellular distribution of cathepsin B. Immunofluorescence results showed that, compared with the control group, DC661-treated cells induced the release of cathepsin B in the lysosome into the cytoplasm ( image 3 A). Hep 3B cells were treated under the above conditions, and the mitochondrial membrane potential was detected by JC-1 fluorescent probe staining. The results of JC-1 fluorescent probe staining showed that compared with the control group, DC661-treated cells showed a trend of decreased red fluorescence and enhanced green fluorescence, indicating that the mitochondrial membrane potential was depolarized ( image 3 B). Cytochrome c in Hep 3B cells was treated under the above conditions for immunofluorescence staining. The...

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Abstract

The invention relates to the field of prevention and / or treatment of hepatocellular carcinoma, in particular to application of DC661 in treatment of hepatocellular carcinoma. Through research, the inventor finds that DC6611 can effectively down-regulate expression of a key molecule HSP70.1 in an HSP70.1 / BMP / ASM pathway for maintaining lysosome membrane stability and inhibit lysosome, so that autophagy is inhibited, tumor cell apoptosis is induced through a mitochondrial pathway, an anti-tumor effect is achieved, and then the application of DC661 in preparation of drugs for preventing and / or treating individual hepatocellular carcinoma is provided. A new choice is provided for treating hepatocellular carcinoma by adopting a non-surgical method.

Description

technical field [0001] The present invention relates to the field of prevention and / or treatment of hepatocellular carcinoma, in particular to the application of DC661 in the treatment of hepatocellular carcinoma. Background technique [0002] DC661 is a recently newly synthesized chloroquine dimer derivative, a potent and highly selective palmitoyl protein thioesterase 1 (PPT1) inhibitor, and has been proven to have antitumor activity. Through bioinformatics analysis, it was found that PPT1 was highly expressed in HCC, and the overall survival of HCC patients with high PPT1 expression was worse. Cox proportional hazards regression analysis showed that PPT1 expression was an independent risk factor for overall survival in HCC patients. Therefore, PPT1 may be a potential molecular target for targeted therapy of HCC. [0003] Studies have demonstrated that DC661 can inhibit lysosomes to inhibit autophagy and produce antitumor activity in vitro and in vivo xenograft tumor mod...

Claims

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Application Information

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IPC IPC(8): A61K31/4709A61P35/00
CPCA61K31/4709A61P35/00
Inventor 徐剑军高杨苏喆邹天浩王为民周星张陈程翔胡少勃宋自芳郑启昌
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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