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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: 2007-06-20
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 Research on the combined effect of Ad-PUMA and chemotherapeutics in various tumor cell lines

[0045] method:

[0046]The PUMA gene is obtained by means known to those skilled in the art and introduced into the adenovirus to obtain Ad-PUMA (Adenovirus-PUMA). Then inoculate cells from the following tumors (breast cancer, cervical cancer, liver cancer, lung cancer, pancreatic cancer) cell lines in the logarithmic growth phase in 96-well plates, adjust the number of cells to be inoculated according to the difference in cell volume between different cell lines, and culture overnight. Before the Ad-PUMA (adenovirus-PUMA) infects the cells, discard the original medium, wash gently with PBS 3 times, and add 100μl serum-free RPMI1640 medium containing a certain amount of Ad-PUMA to make it reach a certain infection Multiplicity of infection means that there are a certain number of infectious Ad-PUMA virus particles in each cell. Due to the differences in the sensitivity...

Embodiment 2

[0052] Example 2 Study on the synergistic effect and mechanism of Ad-PUMA and chemotherapeutics in lung cancer cell lines

[0053] 1. Ad-PUMA significantly reduces the IC50 of different chemotherapeutics in A549 lung cancer cells

[0054] Ad-PUMA10MOI infected A549 cells. After 24 hours, the cells were treated with different concentrations of Taxol, Cisplatin, 5-FU, Etoposide and Adriamycin. After 48 hours, the absorbance of the cells in each well was measured by the MTS method, and the absorbance of each chemotherapeutic agent alone was measured. Calculate the cell growth rate of each treatment group and calculate the IC50 of each chemotherapeutic agent alone and in combination with Ad-PUMA with untreated cells as a control. Each treatment group has 3 parallel holes, and the experiment is repeated 3 times.

[0055] Results Ad-PUMA can significantly reduce the IC50 of various chemotherapeutics in the A549 lung cancer cell line, at least reducing it to 1 / 3 of the original (Adriam...

Embodiment 3

[0063] Example 3 Study on the synergistic effect of Ad-PUMA and chemotherapeutics and its mechanism in esophageal cancer cell lines

[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. Ad-PUMA and Ad-p53 (trade name: "Jinyousheng") of different infection intensity (500MOI~5MOI) were used for recombinant human p53 adenovirus injection. —Produced by Shenzhen Sibo Nuo Gene Technology Co., Ltd., positive control), Ad-GFP (adenovirus with green fluorescent protein gene GFP, negative control) infects various esophageal cancer cells, after 72 hours, the absorbance of cells in each well is measured by MTT Calculate the cell growth rate of each treatment group. Three parallel holes are set for each treatment group, and the experiment is repeated 3 to 4 times.

[0066] The results are shown in Figure 3. It can be seen that in the esophageal cancer cell lines KYSE150, KYSE410, Y...

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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 the new use of PUMA gene, especially the use of the introduction of exogenous PUMA gene or cDNA and protein containing PUMABH3 domain (LRRMADDLN) in preparing drugs that increase tumor sensitivity 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 radical treatment of certain tumors. Post-surgery (adjuvant chemotherapy) and pre-surgery (neoadjuvant chemotherapy) chemotherapy can increase the cure rate of some cancers. , It can increase the chance of surgical resection of a variety of locally advanced solid tumors. However, various chemotherapeutic drugs with different mechanisms of action (alkylating agents, antimetabolites, antitumor antibiotics, antitumor plant drugs, platinum, etc.) have varying degrees of toxic and side effects, such as: bone marrow suppressio...

Claims

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Application Information

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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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