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Application of pharmaceutical composition of metformin and anti-PD-1 antibody in preparation of liver cancer drugs

A technology of metformin and a composition is applied in the application field of preparing liver cancer drugs, which can solve the problems of unfavorable promotion and application, lack of tumor markers, and inability to satisfy both accuracy and practicability.

Pending Publication Date: 2021-05-14
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At this stage, tumor markers used in actual diagnosis and treatment are relatively scarce, such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR ), accuracy and practicability cannot be satisfied at the same time, which is not conducive to clinical promotion and application

Method used

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  • Application of pharmaceutical composition of metformin and anti-PD-1 antibody in preparation of liver cancer drugs
  • Application of pharmaceutical composition of metformin and anti-PD-1 antibody in preparation of liver cancer drugs
  • Application of pharmaceutical composition of metformin and anti-PD-1 antibody in preparation of liver cancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1 A kind of detection method of PSPH protein molecule in liver cancer tissue

[0033] 1. Sample testing

[0034] (1) Select a paraffin section of liver cancer that includes the tumor area, and ensure that there is no large area of ​​necrosis;

[0035] (2) Obtain a 4 μm paraffin section, bake it at 60°C for 2 hours, take it out, and cool it slightly;

[0036] (3) Dewaxing with xylene twice at room temperature, 10 minutes each time;

[0037] (4) Wash away the xylene in 100% ethanol, and then pass through 95% alcohol, 80% alcohol, and 70% alcohol successively, each time for 5 minutes;

[0038] (5) Wash in double distilled water for 5 minutes;

[0039] (6) with 0.3% H 2 o 2 Block endogenous peroxidase activity, room temperature for 10 minutes;

[0040] (7) Wash in double distilled water 4 times, 5 minutes each time;

[0041] (8) Antigen retrieval: 10mM sodium citrate buffer (pH6.0), microwave on high heat for 5 minutes, medium and low heat for 25 minutes; ...

Embodiment 2

[0056] Example 2 Up-regulated expression of PSPH in tumor nests of most liver cancer patients

[0057] 1. Experimental method

[0058] The method of Example 1 was used to detect the expression of PSPH in the paraffin sections of the cancer nest tissues of fresh liver cancer patients.

[0059] 2. Experimental results

[0060] The result is as figure 1 As shown, the results showed that the expression of PSPH (phosphoserine phosphatase) was up-regulated in the tumor nests of most liver cancer patients.

Embodiment 3

[0061] Example 3 In vivo experiments in mice found that the PSPH positive group did not respond to anti-PD-1 antibody treatment

[0062] 1. Experimental method

[0063] 1. The method for establishing the subcutaneous tumorigenesis model of liver cancer in mice is as follows:

[0064] Through the lentiviral transfection system, the expression of PSPH in Hepa1-6 cells was knocked out, and the Hepa1-6 cell line with stable and low expression of PSPH was obtained. The pLKO.1-TCR Cloning Vector plasmid vector was used, and the sh fragment filling region and the shPSPH sequence of the vector were respectively digested by Age1 and EcoR1, and then the shPSPH and the vector were connected to construct a complete knockout plasmid. Hepa1-6 cell line can be stably knocked out of PSPH protein, and the specific sequence of shPSPH is PSPH-shF-CCGGAGGCTGAAGTTCTACTTTTAATCTCGAGATTAAAGTAGAACTTCAGCCTTTTTTG- (the nucleotide sequence is shown in SEQ OD NO: 1), PSPH-shR-AATTCAAAAAAGGCTGAAGTTCTACTTT...

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Abstract

The invention discloses an application of a pharmaceutical composition of metformin and an anti-PD-1 antibody in preparation of a liver cancer drug. According to the invention, immunohistochemical staining is carried out on a tissue sample of a liver cancer patient, and the expression level of PSPH marker protein molecules in liver cancer nest tissue in liver cancer tissue is detected and analyzed; and combined medication of metformin and the anti-PD-1 antibody for PSPH positive patients are guided, and the purpose of improving treatment effect is achieved. When the combined medication of metformin and the anti-PD-1 antibody for patients with high PSPH expression has far better treatment effect than the treatment effect of independent medication of only one selected from metformin and the anti-PD-1 antibody, so precise treatment is achieved, and good treatment effect is achieved.

Description

technical field [0001] The present invention relates to the technical field of biomedicine, in particular, to the application of metformin and anti-PD-1 antibody pharmaceutical composition in the preparation of liver cancer medicine. Background technique [0002] Primary liver cancer is the sixth most common cancer in the world, and its death rate ranks third among all kinds of malignant tumors. China is an area with a high incidence of liver cancer, and hepatitis B virus infection is the main factor of the high incidence of liver cancer in my country, which seriously endangers human life and health. At present, the clinical treatment for liver cancer is mostly radical resection. For patients who cannot be surgically resected, targeted drug therapy commonly used in clinical practice is often used, but the treatment effect is not ideal. At the same time, during the occurrence and development of tumors, the immune system also plays an important role in the occurrence and deve...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K31/155A61P1/16A61P35/00G01N33/574
CPCA61K31/155A61K39/3955A61P1/16A61P35/00G01N33/57484G01N33/57438A61K2039/505A61K2300/00
Inventor 吴艳郑利民彭志鹏
Owner SUN YAT SEN UNIV
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