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Application of adrb2 inhibitor in combination with sorafenib in the preparation of drugs for the treatment of liver cancer

A technology for the treatment of liver cancer and receptor inhibitors, applied in the field of medicine, can solve the problem of unclear β2 adrenergic receptors and other problems, and achieve the effects of inhibiting proliferation and clone formation, inhibiting growth, and being easy for clinical promotion and use.

Active Publication Date: 2018-07-20
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of β2 adrenergic receptor (ADRB2) inhibitors in the treatment of liver cancer is still unclear, and there is no literature report on the role of combined ADRB2 inhibitors and sorafenib in the treatment of liver cancer

Method used

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  • Application of adrb2 inhibitor in combination with sorafenib in the preparation of drugs for the treatment of liver cancer
  • Application of adrb2 inhibitor in combination with sorafenib in the preparation of drugs for the treatment of liver cancer
  • Application of adrb2 inhibitor in combination with sorafenib in the preparation of drugs for the treatment of liver cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Liver cancer cell lines SMMC-7721, HepG2, and PVTT were introduced into 96-well plates, with 3,000 cells per well. Each type of cells was divided into two groups, DMSO and ICI, with 5 auxiliary wells in each group. After the cells adhered to the wall, it was counted as time 0, and each group was given 10 μM DMSO or ICI respectively. The medium was sucked off at 0, 24, 48, 72, and 96 hours respectively, and 10% CCK8 detection reagent diluted with DMEM was added, and the absorbance value at 450 nm was detected after incubating at 37° C. for 1 hour. Growth curves were drawn using the absorbance values ​​measured at each time point.

[0038] Depend on figure 1 In middle A, it can be seen that ICI can significantly slow down the proliferation rate of liver cancer cells within 24 hours, and this trend becomes more and more significant as time goes on.

[0039]In order to further prove that ICI can inhibit the proliferation of liver cancer cells, we conducted cell cloning ex...

Embodiment 2

[0042] The liver cancer cell line PVTT was introduced into a 12-well plate, and the cell density was about 50%. After the cells adhered to the wall, add 15 μL each of the control lentivirus or two shADRB2 viruses with different interference sites to the cell culture medium suspension, and shake well. After 8 hours, the medium was changed, and after 24 hours, puromycin with a concentration of 5 μM was added to continue the cultivation. When the cell density reached 100%, the cells were transferred to a 6-well plate and continued to cultivate. After identifying the interference effect by RT-PCR, the cells were introduced into a 96-well plate with 3000 cells per well. After the cells adhered to the wall, it was counted as 0 time, and the medium was sucked off at 0, 24, 48, 72, and 96 hours respectively, and 10% CCK8 detection reagent diluted with DMEM was added, and the absorbance at 450nm was measured after incubating at 37°C for 1 hour. value. Growth curves were drawn using t...

Embodiment 3

[0045] The liver cancer cell lines SMMC-7721, HepG2 and HMCC-LM3 were introduced into 96-well plates with 5000 cells per well. After the cells adhered to the wall, they were divided into four groups, with 5 auxiliary wells in each group, and each group was replaced with the medium containing the following drugs:

[0046] 1) DMSO;

[0047] 2) ICI 20μM;

[0048] 3) Sorafenib 20μM+DMSO;

[0049] 4) Sorafenib 20 μM + ICI 20 μM.

[0050] After incubation in a 37°C incubator for 24h, the culture medium was sucked off, and 10% CCK8 detection reagent diluted with DMEM was added, and the absorbance value at 450nm was detected after incubation in a 37°C incubator for 1h. Based on the absorbance value detected in the first group, calculate the inhibition rate of cells in groups 2-4, and draw a histogram of growth inhibition.

[0051] Depend on image 3 It can be seen that ICI combined with Sorafenib can significantly increase Sorafenib's growth inhibition on liver cancer cells, and ...

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Abstract

The invention relates to the field of a medical technology. In recent years, the beta2 adrenocepter (ADRB2) and its signal pathway have been given more and more attention in the cancer prevention and treatment research field. The invention provides an application of the ADRB2 inhibitor in the preparation of a medicine for treating liver cancer. Especially, the ADRB2 inhibitor and sorafenib can be combined to effectively inhibit growth of liver cancer and effectively inhibit efficiency of tumor forming by transplantation of liver cancer so as to reduce evolution of liver cancer. The application is easy for clinical application and popularization.

Description

Technical field: [0001] The invention relates to the technical field of medicine, in particular to the application of an ADRB2 inhibitor combined with sorafenib in the preparation of a drug for treating liver cancer. Background technique: [0002] Primary hepatocellular carcinoma (HCC) is the fifth most common tumor and the third leading cause of cancer-related death in the world. Hepatocellular carcinoma is common in developing countries, especially in East Asia, Southeast Asia, the Pacific Basin, and sub-Saharan Africa. Of the 626,000 reported cases of HCC, approximately 410,000 were in East Asia (346,000 in China and 40,000 in Japan). However, HCC has a poor prognosis due to the higher incidence of invasion and metastasis before treatment. [0003] Sorafenib is a multi-target anti-tumor drug jointly developed by Bayer and Onyx, which can significantly inhibit tumor proliferation and angiogenesis. It is the first targeted drug approved by the US FDA for the clinical trea...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61K31/7088A61K31/138A61P35/00A61K33/24A61K31/44A61K31/704
Inventor 王红阳杨文邬福全梁东吕桂帅方田于乐兴
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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