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Application of CXCR2 inhibitor in preparation of medicine for treating nasopharynx cancer

A nasopharyngeal cancer and inhibitor technology, applied in the field of medicine, can solve the problems of poor treatment effect, intolerable side effects, and affecting the normal development of combination therapy in patients with advanced nasopharyngeal cancer.

Active Publication Date: 2021-06-25
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Reported data have shown that the 3-year local control rate and survival rate of early and locally advanced nasopharyngeal carcinoma can reach 80-90%, but the treatment effect of advanced nasopharyngeal carcinoma patients is still poor , its 3-year survival rate is about 25-58%
At the same time, despite the continuous improvement of radiotherapy technology, due to the anatomical location of nasopharyngeal carcinoma close to radiation-sensitive organs, such as salivary glands, optic chiasm, cochlea, brainstem and temporal lobe, acute reactions such as mucosal inflammation and vomiting caused by radiotherapy and 2 -Late side effects such as grade 4 dry mouth (39.3%), hearing loss (37.0%), optic nerve damage (20%), and temporal lobe necrosis (5%) are still unavoidable
In addition, the hematological and non-hematological toxicities associated with platinum-based concurrent chemoradiotherapy (CRT) also seriously reduce the quality of life of patients
Some patients are unable to tolerate the side effects, which affect the normal development of combination therapy

Method used

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  • Application of CXCR2 inhibitor in preparation of medicine for treating nasopharynx cancer
  • Application of CXCR2 inhibitor in preparation of medicine for treating nasopharynx cancer
  • Application of CXCR2 inhibitor in preparation of medicine for treating nasopharynx cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Example 1 Expression of CXCR2 and its ligand CXCL8 in nasopharyngeal carcinoma

[0083] 1.1 High expression of CXCR2 in tumor cells and stromal cells in nasopharyngeal carcinoma patients is associated with poor prognosis

[0084] Through immunohistochemical staining on the tumor pathological tissue chips of 99 nasopharyngeal carcinoma patients provided by Shanghai Xinchao Biotechnology Co., Ltd., it was found that both tumor cells and stromal cells in the nasopharyngeal carcinoma tissues expressed the chemokine CXCR2, such as figure 1 Shown in A, where brown represents positive expression, and the magnification of the figure is 20 times.

[0085] According to the expression intensity and positive rate of CXCR2, two researchers performed independent immunohistochemical analysis (IHC) scores on the expression of CXCR2, and divided them into tumor cells with high CXCR2 expression group and tumor cell CXCR2 high expression group and tumor cells according to the location of ...

Embodiment 2

[0094] Example 2 In vitro experiment of CXCR2 inhibitor SB225002 inhibiting the proliferation of human nasopharyngeal carcinoma cells 2.1 SB225002 inhibits the activity of human nasopharyngeal carcinoma cells

[0095] In vitro, different concentrations of SB225002 (0 μM, 0.25 μM, 0.5 μM, 1 μM) were applied to the above human nasopharyngeal carcinoma cell lines (C666-1, HONE-1, HNE-1, CNE-1, CNE-2), After 24 hours, the morphology and growth status of tumor cells were observed. It was found that as the concentration increased, C666-1 and HONE-1 cells gradually became rounder and brighter, and their floating increased. After treatment at a concentration of 1 μM, most of the cells floated in the medium ; Some of the HNE-1 cells treated with 1 μM concentration became bright and round, and floated in the culture medium; while the morphological changes of CNE-1 and CNE-2 cells were not obvious, such as Figure 4 As indicated, the scale bar is 500 μm.

[0096] In vitro, different con...

Embodiment 3

[0106] Example 3 In vitro experiment of CXCR2 inhibitor SB225002 inhibiting angiogenesis

[0107] 3.1SB225002 inhibits the chemotaxis of human nasopharyngeal carcinoma cell tumor supernatant to HUVECs

[0108] In order to explore the effect of CXCR2 inhibitor SB225002 on angiogenesis in nasopharyngeal carcinoma tumors, human nasopharyngeal carcinoma cell tumor supernatant (tumor culture medium supernatant, TS) and human recombinant protein CXCL8 were used to stimulate human umbilical vein in vitro. Epithelial cells (HUVECs), the inhibitory effect of SB225002 on the migration ability of HUVECs in Transwell was measured. Inoculate 1 × 10 in the upper chamber of the Transwell 5 HUVECs per 200ul, the lower chamber was added with or without SB225002 (0.5μM) human nasopharyngeal carcinoma cell tumor supernatant, 50ng / ml human recombinant protein CXCL8 and serum-free antibiotic-free DMEM medium, cultured for 24 hours Afterwards, the cells were fixed with 4% paraformaldehyde, staine...

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Abstract

The invention relates to an application of a CXCR2 inhibitor in preparation of a medicine for treating nasopharynx cancer, and belongs to the field of medicine. The invention provides an application of a CXCR2 inhibitor in preparation of a medicine for treating nasopharynx cancer or preventing nasopharynx cancer relapse, an application in preparation of a radiotherapy sensitizer for nasopharynx cancer and an application in preparation of a radiotherapy protective agent for nasopharynx cancer. The application of the invention is helpful for reducing toxic and side effects caused by clinical radiation therapy of nasopharyngeal carcinoma, improving the life quality of nasopharyngeal carcinoma patients and the curative effect of advanced nasopharyngeal carcinoma patients, and providing a new thought and strategy for comprehensive treatment of nasopharyngeal carcinoma clinically.

Description

technical field [0001] The invention relates to the use of a CXCR2 inhibitor in the preparation of medicines for treating nasopharyngeal carcinoma, which belongs to the field of medicine. Background technique [0002] Nasopharyngeal carcinoma is a malignant tumor originating from nasopharyngeal epithelial cells, which is closely related to EBV infection. Nasopharyngeal carcinoma is one of the malignant tumors with high incidence in southern China, where the annual incidence rate can reach 20-30 / 100000. The current treatment plan for nasopharyngeal carcinoma is a comprehensive treatment plan based on radiotherapy and supplemented by platinum-based chemotherapy. Early stage patients can achieve complete remission only by radiotherapy, and patients with locally advanced disease need to receive intensive treatment with concurrent chemotherapy and radiotherapy (Chemoradiation therapy, CRT). With the continuous improvement of the level of radiation therapy, intensity-modulated r...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/17A61P35/00
CPCA61K45/00A61K31/17A61P35/00
Inventor 魏霞蔚刘晓蓓魏于全
Owner SICHUAN UNIV
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