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Use of PUMA in tumor chemoradiotherapy sensibilization

A kind of use, the technology of radiotherapy, applied in the new use field of PUMA in the sensitization of tumor radiotherapy and chemotherapy

Inactive Publication Date: 2012-01-25
CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These toxic and side effects have seriously affected the clinical application of radiotherapy and chemotherapy. It is the goal of medical workers to find a substance that can enhance the curative effect of radiotherapy and chemotherapy and reduce its therapeutic dose, thereby reducing its toxic and side effects.

Method used

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  • Use of PUMA in tumor chemoradiotherapy sensibilization
  • Use of PUMA in tumor chemoradiotherapy sensibilization
  • Use of PUMA in tumor chemoradiotherapy sensibilization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1 Study on the Combined Effects of Ad-PUMA and Chemotherapeutic Drugs in Various Tumor Cell Lines

[0045] method:

[0046] The PUMA gene was obtained by means known to those skilled in the art, and introduced into adenovirus to obtain Ad-PUMA (adenovirus-PUMA). Then the following various tumors (breast cancer, cervical cancer, liver cancer, lung cancer, pancreatic cancer) cell line cells in the logarithmic growth phase were inoculated in 96-well plates, and the number of inoculated cells was adjusted according to the difference in cell volume between different cell lines, and cultured overnight. Before the Ad-PUMA (adenovirus-PUMA) infects the cells, discard the original culture medium, gently wash it 3 times with PBS, and add 100 μl of serum-free RPMI1640 medium containing a certain amount of Ad-PUMA to achieve a certain degree of infection. Multiple (multiplicity of infection), that is, there is a certain number of infectious Ad-PUMA virus particles in ea...

Embodiment 2

[0052] Example 2 Study on the Synergistic Effect of Ad-PUMA and Chemotherapeutic Drugs in Lung Cancer Cell Lines and Its Mechanism

[0053] 1. Ad-PUMA significantly reduced the IC50 of different chemotherapeutic drugs in A549 lung cancer cells

[0054] Infect A549 cells with Ad-PUMA10MOI, treat the cells with different concentrations of Taxol, Cisplatin, 5-FU, Etoposide, and Adriamycin after 24 hours, continue to culture for 48 hours, and then use the MTS method to detect the absorbance of the cells in each well, and at the same time detect the absorbance of each chemotherapeutic drug alone Using untreated cells as a control, calculate the growth rate of cells in each treatment group, and calculate the IC50 of each chemotherapeutic drug alone and in combination with Ad-PUMA. Three parallel wells were set up for each treatment group, and the experiment was repeated 3 times.

[0055] Results In the A549 lung cancer cell line, Ad-PUMA can significantly reduce the IC50 of vario...

Embodiment 3

[0063] Example 3 Study on the Synergistic Effect of Ad-PUMA and Chemotherapeutic Drugs in Esophageal Cancer Cell Lines and Its Mechanism

[0064] 1. Ad-PUMA inhibits the growth and proliferation of different esophageal cancer cell lines

[0065] Ad-PUMA was obtained by the same method as in Example 1, and Ad-PUMA and Ad-p53 (trade name: "Jin Yousheng", recombinant human p53 adenovirus injection) with different infection intensities (500MOI-5MOI) were used respectively. —Manufactured by Shenzhen Saibainuo Gene Technology Co., Ltd., positive control), Ad-GFP (adenovirus with green fluorescent protein gene GFP, negative control) to infect various esophageal cancer cells, and after 72 hours, MTT was used to detect the absorbance of cells in each well , calculate the cell growth rate of each treatment group. Three parallel wells were set up for each treatment group, and the experiment was repeated 3 to 4 times.

[0066] see attached results image 3 . It can be seen that in t...

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Abstract

An application of external PUMA gene or the cDNA or protein containing PUMA BH3 structure domain in preparing the sensitive medicine for radiotherapy or chemicotherapy of cancer cells is disclosed.

Description

technical field [0001] The present invention relates to a new use of PUMA gene, especially the use of introducing exogenous PUMA gene or cDNA and protein containing PUMABH3 domain (LRRMADDLN) in the preparation of medicines for increasing the sensitivity of tumors to chemotherapeutics and radiotherapy. Background technique [0002] Tumor chemotherapy is an indispensable and important method in the comprehensive treatment of malignant tumors. It has become the main method for the radical cure of certain tumors. Post-operative (adjuvant chemotherapy) and pre-operative (neoadjuvant chemotherapy) chemotherapy can improve the cure rate of some cancers , can increase the chance of surgical resection of locally advanced solid tumors. However, various chemotherapy drugs with different mechanisms of action (alkylating agents, anti-metabolite drugs, anti-tumor antibiotics, anti-tumor plant drugs, platinum, etc.) have different degrees of toxic and side effects, such as: bone marrow su...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61K45/00A61K31/7068A61K38/16A61P35/00
Inventor 林晨詹启敏王海娟张林余健
Owner CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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