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Composition for cancer radiotherapy sensitization and application thereof

A composition and cancer technology, applied in the field of tumor, can solve the problems of no research results and insufficient excavation, and achieve the effect of effective treatment strategy, major clinical and socio-economic significance

Inactive Publication Date: 2020-07-24
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the application of these PIs in cancer treatment, especially in combination with radiation therapy, has not been fully explored, especially in esophageal cancer, throat cancer, cervical cancer, anal canal cancer, etc. Cancer types, and colorectal cancer, breast cancer, lymphoma, brain metastases and other cancer types that use radiotherapy as an adjuvant method have no corresponding research results

Method used

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  • Composition for cancer radiotherapy sensitization and application thereof
  • Composition for cancer radiotherapy sensitization and application thereof
  • Composition for cancer radiotherapy sensitization and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Tumor Synergistic Inhibition Experiment

[0039] Four kinds of cells including HT-29, HCT116, SW837 and FaDu were selected, and bortezomib (BTZ), elsazomib (IXZ) and carfilzomib (CFZ) were selected as proteasome inhibitors (PIs) for the experiment. The effect of radiotherapy on cell proliferation is mainly reflected by the clone formation ability of cells. The specific experimental methods are as follows:

[0040]HCT116, HT29, SW837 and FaDu cells were seeded into 6-well plates at a density of 1000 cells / well. After 24 hours, cells were treated with indicated doses of X-rays or drugs, then cultured for 10–14 days, fixed with methanol, and stained with 0.5% crystal violet. Colonies containing more than 50 cells were counted.

[0041] The results showed that low concentrations of BTZ, IXZ, and CFZ could significantly weaken the colony formation ability of HT29, HCT116, SW837, and FaDu cells after radiotherapy (such as figure 1 As shown), and with the increase...

Embodiment 2

[0048] Example 2 DNA double-strand breaks (DSBs) damage and cell apoptosis experiment

[0049] The most direct effect of radiotherapy is to cause DNA double-strand breaks. Based on the above obvious synergistic effects, the degree of DNA damage is further judged by the comet experiment. In this experiment, three cell lines, HT-29, HCT116 and SW837, were selected, and bortezomib (BTZ) was selected as proteasome inhibitors (PIs). The specific experimental method is as follows:

[0050] The cells were first treated with PIs for 12 hours, then irradiated with X-rays (6Gy), cultured for 6 hours, and then collected with a comet assay kit (4250-050-K, Trevigen, Gaithersburg, MD, USA) and cultured at 3× 10 5 Cells / mL were resuspended in PBS for DNA damage analysis. Comet experiments were then performed according to the manufacturer's instructions. After PI staining, comet images were taken with a fluorescence microscope. The average comet tail moment (percentage of DNA in the tai...

Embodiment 3

[0056] Example 3 In vivo tumor suppression experiment

[0057] HCT116 cells were transplanted into tumor blocks (approximately 5mm 3 ) were implanted subcutaneously on the right side of nude mice to establish xenograft models, and were randomly divided into 4 groups: BTZ-radiotherapy X-ray combined treatment group, normal saline (NS)-radiotherapy X-ray combined group, BTZ group, and normal saline (NS) group . The BTZ-X-ray combined therapy group and the normal saline (NS)-radiotherapy X-ray combined group were given BTZ (0.1 mg / kg / day × 7 days) and X-ray radiation every other day in turn from the 7th day after the tumor was planted. Treatment, BTZ group and normal saline (NS) group were administered in the same manner as the first two groups, but no radiation therapy was performed, the tumor volume was measured once a week, and the treatment cycle was 14 days. After 3 weeks of treatment, the mice were sacrificed to remove the tumor mass ( Tumors such as Figure 6 shown).

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Abstract

The invention provides a composition for cancer radiotherapy sensitization and application thereof. The composition comprises one or more proteasome inhibitors. Researches show that the proteasome inhibitors, especially 20S CP inhibitors, can block DSB, have a significant synergistic effect on tumor radiotherapy, and effectively solve the problems of low radiotherapy sensitivity, not significant curative effect and large side effect in existing clinical treatment. The clinical use of the proteasome inhibitors can significantly improve the radiotherapy sensitivity of tumor patients, thereby greatly improving the therapeutic effect of the tumor patients.

Description

technical field [0001] The invention belongs to the field of tumors, and in particular relates to a composition for cancer radiosensitization and its application. Background technique [0002] Chemoradiotherapy, which accounts for a large proportion of current cancer treatment modalities, significantly increases the control rate of local progression and leads to clinical and histological tumor regression. However, because the treatment is limited by indications, contraindications, drug resistance and high-dose side effects, the curative effect is not ideal. Therefore, it has become a current research hotspot to study new therapeutic strategies combined with radiotherapy and chemotherapy to improve the sensitivity of cancer patients. At the same time, it is necessary and urgent to study the mechanism of their combined effects. For example, in the treatment of colorectal cancer, radiotherapy is one of the important methods in the comprehensive treatment of colorectal cancer, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K45/00A61K38/05A61K38/08A61P35/00
CPCA61K41/0038A61K45/00A61K38/08A61K38/05A61P35/00
Inventor 岳欣刘然义王雪涔刘听雨
Owner SUN YAT SEN UNIV CANCER CENT
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