Flotilli-2 as target in screening nasopharyngeal carcinoma metastasis inhibiting drugs and application of Flotilli-2

A technology of flotillin-2, 2.flotillin-2, which is applied in the field of function and application of genes and proteins, and can solve the problem that the specific mechanism of nasopharyngeal carcinoma is not very clear.

Inactive Publication Date: 2015-07-08
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the specific mechanism by which Flo

Method used

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  • Flotilli-2 as target in screening nasopharyngeal carcinoma metastasis inhibiting drugs and application of Flotilli-2
  • Flotilli-2 as target in screening nasopharyngeal carcinoma metastasis inhibiting drugs and application of Flotilli-2
  • Flotilli-2 as target in screening nasopharyngeal carcinoma metastasis inhibiting drugs and application of Flotilli-2

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1: Flot2 is highly expressed in nasopharyngeal carcinoma tissues, and is associated with lymph nodes and distant metastasis.

[0066] 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 ).

[0067] 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.

[0068] All patients were grouped by T stage, N stage, M sta...

Embodiment 2

[0069] Example 2: Increased expression of Flot2 predicts poor prognosis for patients with nasopharyngeal carcinoma.

[0070] 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).

[0071] Table 1: Clinical characteristics and related univariate survival regression analysis of patients with nasopharyngeal carcinoma in this study

[0072] variable

Number of cases

5-year survival rate (%)

P value

gender

0.679

Female

68

48(70.6％)

male

113

78(69.0％)

...

Embodiment 3

[0080] Example 3: TGF-β induces EMT by activating Src.

[0081] 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.

[0082] 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 ).

[0083] 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 ).

[0084] Similarly, in the Transwell experiment, we obtained similar results...

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Abstract

The invention belongs to the fields of functions and applications of gene and protein, and relates to Flotilli-2 as a target in screening nasopharyngeal carcinoma metastasis inhibiting drugs and an application of the Flotillin-2. The invention provides a target for screening nasopharyngeal carcinoma metastasis inhibiting drugs, wherein the target is Flotillin-2. The invention also provides an application of the Flotillin-2 as a drug target in screening nasopharyngeal carcinoma metastasis inhibiting drugs. The invention also provides a drug for inhibiting nasopharyngeal carcinoma metastasis, which takes the Flotillin-2 as a target. The drug is siRNA of Flotillin-2. The invention discloses the relation between the Flotillin-2 (Flot2) and a TGF-beta signal path in nasopharyngeal carcinoma as well as effects of the Flot2 and the TGF-beta signal path in nasopharyngeal carcinoma metastasis for the first time. In the nasopharyngeal carcinoma, the Flot2 is an independent predictive factor of patient poor prognosis, an important component of the TGF-beta signal path and an indispensable important node in a process of stimulating emergency medical treatment (EMT). Silent Flot2 may become one of important means of resisting EMT caused by TGF-beta. Therefore, the invention provides a theoretical foundation and a clinical base for researching a new target and a new strategy in inhibiting nasopharyngeal carcinoma metastasis.

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 t...

Claims

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Application Information

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IPC IPC(8): C12Q1/68A61K48/00A61K31/7088A61P35/04
Inventor 廖旺军林立赵亮潘常惬石敏廖禹林宾建平
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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