Flotillin-2 as a target for screening drugs that inhibit the metastasis of nasopharyngeal carcinoma and its application

A nasopharyngeal cancer and drug technology, applied in the field of gene and protein function and application, can solve the problem that the specific mechanism of nasopharyngeal cancer is not very clear

Inactive Publication Date: 2018-12-28
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the specific mechanism by which Flot2 promotes NPC metastasis is still unclear.

Method used

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  • Flotillin-2 as a target for screening drugs that inhibit the metastasis of nasopharyngeal carcinoma and its application
  • Flotillin-2 as a target for screening drugs that inhibit the metastasis of nasopharyngeal carcinoma and its application
  • Flotillin-2 as a target for screening drugs that inhibit the metastasis of nasopharyngeal carcinoma and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Example 1: Flot2 is highly expressed in nasopharyngeal carcinoma tissues, and is associated with lymph nodes and distant metastasis.

[0065] The expression of Flot2 was evaluated on paraffin tissue samples of 181 patients with nasopharyngeal carcinoma by immunohistochemistry (IHC). The results showed that Flot2 was mainly distributed on the cell membrane, and its expression level in nasopharyngeal carcinoma tissues was significantly higher than that in adjacent normal tissues ( Figure 1A ).

[0066] According to the depth of Flot2 staining, all patients were divided into 3 groups, negative group (0-2 points), weak positive group (3-5 points), strong positive group (greater than 5 points). Among 181 NPC patients, a total of 112 were positive for Flot2, a significant majority of positive cases compared to 69 negative patients. Of the 112 positive cases, 72 were weakly positive and 40 were strongly positive.

[0067] All patients were grouped by T stage, N stage, M sta...

Embodiment 2

[0068] Example 2: Increased expression of Flot2 predicts poor prognosis for patients with nasopharyngeal carcinoma.

[0069] Through the COX survival analysis regression model, we analyzed the univariate correlation analysis including age, sex, Flot2 score, T stage, N stage, M stage and TNM total stage and the prognosis of patients with nasopharyngeal carcinoma. We found that Flot2 score, N stage, M stage and TNM total stage can significantly affect the prognosis of NPC patients. Age, gender, and T stage had no significant predictive significance for the prognosis of patients with nasopharyngeal carcinoma (Table 1).

[0070] Table 1: Clinical characteristics and related univariate survival regression analysis of patients with nasopharyngeal carcinoma in this study

[0071] variable

Number of cases

5-year survival rate (%)

P value

gender

0.679

Female

68

48(70.6％)

male

113

78(69.0％)

age)

...

Embodiment 3

[0079] Example 3: TGF-β induces EMT by activating Src.

[0080] Considering that TGF-β-induced EMT has been rarely studied in NPC, we first needed to determine whether stimulation of TGF-β has the ability to induce EMT in NPC cell lines. Therefore, TGF-β was added to nasopharyngeal carcinoma cell lines.

[0081] In the CNE-1 cell line, we noticed that TGF-β caused changes in cell morphology, becoming scattered growth cells with multiple pseudopod-shaped protrusions and irregular shapes ( Figure 3A ). After using TGF-β type I receptor blocker SB431542 or Src activity inhibitor PP2, the above-mentioned morphological changes were reversed ( Figure 3A ).

[0082] In the scratch test, the migration ability of cells was significantly enhanced by TGF-β, but under the action of SB431542 or PP2, the migration ability of cells was not significantly different from that of the control group ( Figure 3B ).

[0083] Similarly, in the Transwell experiment, we obtained similar results...

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Abstract

The invention belongs to the functions and the application field of genes and albumen, and relates to a target for screening and restraining the transfer of nasopharyngeal carcinoma by using Flotillin-2 as a medicine and application of the target. The invention provides the target for screening and restraining the transfer of the nasopharyngeal carcinoma, and the target is the Flotillin-2. The invention also provides the application of the Flotillin-2 as the medical target in the medicine for screening and restraining the transfer of the nasopharyngeal carcinoma. The invention also provides the medicine for restraining the transfer of the nasopharyngeal carcinoma by using the Flotillin-2 as the target. The medicine is siRNA of Flotillin-2. The invention firstly reveals the relationship between Flotillin-2(Flot2) and a TGF-beta signal route in the nasopharyngeal carcinoma and the effect of the Flotillin-2(Flot2) and the TGF-beta signal route in the transfer of the nasopharyngeal carcinoma. The Flot2 is an independent predictive factor for the poor prognosis of a patient in the nasopharyngeal carcinoma, is an important constituent part of the TGF-beta route, and is an indispensable important node in the process of promoting EMT. The silent Flot2 may become one of important means for opposing the EMT caused by TGF-beta. Therefore, the invention provides a theory basis and a clinical base for researching new target points and new policies for restraining the transfer of the nasopharyngeal carcinoma.

Description

technical field [0001] The invention belongs to the field of functions and applications of genes and proteins, and relates to the new application of Flotillin-2, in particular to Flotillin-2 as a target for screening drugs for inhibiting the metastasis of nasopharyngeal carcinoma and its application. Background technique [0002] In epithelial tumor tissue, tumor cells usually still have the cell polarity of epithelial tissue, and the cells are bound by tight intercellular junctions. During epithelial-mesenchamal transition (EMT), cells gradually lose many characteristics of typical epithelial cells, and acquire some characteristics of mesenchymal cells, causing a series of subsequent tumor cell invasion and metastasis events. This process is controlled by a series of extracellular and intracellular signaling molecules. Transforming growth factor-β (transforming growth factor-β) is an extracellular growth factor that has been shown to promote the metastasis of a variety of ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6886A61K48/00A61K31/713A61P35/04
CPCA61K31/713A61K48/00C12Q1/6886C12Q2600/136
Inventor 廖旺军林立赵亮
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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