阅读说明：本技术 一种咔啉衍生物用于制备治疗甲状腺癌的药物用途 (Application of carboline derivative in preparation of medicine for treating thyroid cancer ) 是由 不公告发明人 于 2020-08-12 设计创作，主要内容包括：本发明公开了一种咔啉衍生物用于制备治疗甲状腺癌的药物用途。本领域技术人员知道,传统化疗药物对甲状腺肿瘤普遍疗效不够显著。本发明通过研究发现,咔啉衍生物既可以抑制甲状腺癌TP-1细胞的生长增殖,又可以抑制其迁移活性,因此,咔啉衍生物具有开发成抑制甲状腺癌生长和/或转移的抗肿瘤药物。(The invention discloses an application of carboline derivatives in preparing a medicament for treating thyroid cancer. Those skilled in the art know that conventional chemotherapeutic drugs are not generally effective enough for thyroid tumors. According to the invention, researches show that the carboline derivative can inhibit the growth and proliferation of thyroid cancer TP-1 cells and the migration activity of the thyroid cancer TP-1 cells, so that the carboline derivative can be developed into an antitumor drug for inhibiting the growth and/or metastasis of thyroid cancer.)

1. An application of carboline derivative with the following structure in preparing anti-thyroid cancer drugs.

2. An application of carboline derivative with the following structure in preparing a medicine for resisting the proliferation and growth of thyroid cancer.

3. An application of carboline derivative with the following structure in preparing a drug for resisting invasion and metastasis of thyroid cancer.

4. An antithyroid pharmaceutical preparation characterized by: carboline derivatives with the following chemical structures are used as active ingredients, and pharmaceutically acceptable auxiliary materials are used for preparing pharmaceutically acceptable dosage forms.

5. The pharmaceutical formulation of claim 4, wherein: the auxiliary materials comprise common liquid auxiliary materials and solid auxiliary materials or semisolid auxiliary materials.

6. The pharmaceutical formulation of claim 4, wherein: the dosage forms comprise common tablets, capsules, injections and granules.

Technical Field

The invention belongs to the field of medicines, and relates to an application of carboline derivatives in preparing a medicine for treating thyroid cancer.

Background

Thyroid cancer belongs to endocrine malignancies, and is the most common thyroid malignancy. The general curative effect of the traditional chemotherapy drugs on thyroid tumors is not obvious enough, the postoperative immune function of patients is often influenced by operation and radiotherapy which are the current clinical preferred treatment modes, and the recurrence rate of the patients is higher.

Therefore, there is a need to continuously search for the development of anti-thyroid cancer chemotherapeutic drugs with significant efficacy.

Disclosure of Invention

The invention aims to provide application of carboline derivatives in preparing medicaments for treating thyroid cancer.

The technical scheme for realizing the aim of the invention is as follows:

an application of carboline derivative with the following structure in preparing anti-thyroid cancer drugs.

An application of carboline derivative with the following structure in preparing a medicine for resisting the proliferation and growth of thyroid cancer.

An application of carboline derivative with the following structure in preparing a drug for resisting invasion and metastasis of thyroid cancer.

A pharmaceutical preparation for treating thyroid cancer comprises carboline derivatives with the following chemical structures as active ingredients, and pharmaceutically acceptable adjuvants.

Preferably, the auxiliary materials comprise common liquid auxiliary materials and solid auxiliary materials, or semisolid auxiliary materials.

Preferably, the dosage form comprises commonly used tablets, capsules, injections and granules.

The invention has the outstanding advantages that:

those skilled in the art know that conventional chemotherapeutic drugs are not generally effective enough for thyroid tumors. According to the invention, researches show that the carboline derivative can inhibit the growth and proliferation of thyroid cancer TP-1 cells and the migration activity of the thyroid cancer TP-1 cells, so that the carboline derivative can be developed into an antitumor drug for inhibiting the growth and/or metastasis of thyroid cancer.

Drawings

FIG. 1 shows the chemical structure of carboline compounds.

FIG. 2 is a set of representative migration patterns in cell migration assays.

Detailed Description

The following detailed description of the present invention is provided in connection with the examples, and for reasons of brevity, the description of the experimental procedures is not intended to be exhaustive, and all parts not specifically described in the experiments are routine procedures well known to those skilled in the art.

First, experimental material

Thyroid carcinoma TP-1 cells were purchased from ATCC, cultured in RPMI-1640 containing 10% fetal bovine serum at 37 ℃ under 5% CO₂And (5) performing conventional culture in a cell culture box.

RPMI-1640 medium and fetal bovine serum were purchased from Gibco, USA.

The chemical structure of the carboline derivative to be tested is shown in figure 1, and the purity is 99.3%.

Second, Experimental methods

1. Cell proliferation Activity assay

Digesting and re-suspending TP-1 cells of thyroid cancer in logarithmic growth phase to prepare cell suspension, and inoculating the cell suspension into a 96-well plate, wherein each well is 1 × 10⁴Cell, 200. mu.L, 37 ℃ and 5% CO₂Culturing under the condition for 24h, replacing with RPMI-1640 medium containing 100, 200, 500nM carboline derivatives and 10% fetal calf serum, and culturing for 48h while setting blank control groups without drug, each 5 multiple wells. After the time, 20 mu L of MTT reagent with the concentration of 5mg/mL is added into each well, the culture is continued for 4h, the supernatant is discarded, 150 mu L of DMSO is added into each well, the mixture is shaken and dissolved, the absorbance value (OD570) at the wavelength of 570nm is measured by an enzyme-linked immunosorbent assay, and the proliferation activity of the thyroid cancer TP-1 cells of each drug group is calculated according to the following formula by taking the proliferation activity of the thyroid cancer TP-1 cells of a blank control group as 100 percent.

Cell proliferation activity (%) ═ drug group OD 570/blank control group OD 570X 100%

2. Cell migration Activity assay

Taking thyroid cancer TP-1 cells in logarithmic growth phase, digesting and re-suspending the cells to prepare a cell suspension, and adding 1.5 × 10⁵one/mL of the concentration was plated in 6-well plates, with 1mL per well. After 48h, cells were essentially confluent in 6-well plates. Marking scratches with consistent width in 6-well plate with sterile 200 μ L pipette tip, cleaning culture medium for 3 times, washing off scratched cells, adding serum-free culture medium containing medicine or solvent, and separating into carboline derivativesBiological group and control group, wherein the carboline derivative group contains 500nM carboline derivative, the control group is replaced by equal volume of solvent at 37 deg.C and 5% CO₂And (3) taking out the 6-hole plate after the conditional culture is carried out for 24h, selecting the same position as much as possible, taking a picture under a microscope, measuring the distance between scratches, and calculating the migration inhibition rate of the drug on the thyroid cancer TP-1 cells according to the following formula. Each group of 3 multiple wells.

Migration inhibition (%) was ═ distance between drug scratches-distance between controls ÷ distance between controls scratches × 100%

3. Statistical method

All data were statistically analyzed using SPSS 17.0, the data were expressed as mean. + -. standard deviation, the comparison between the two groups was performed using t-test, and the difference P < 0.05 was statistically significant.

Third, experimental results

1. Measurement of cell proliferation Activity

As shown in table 1, the OD570 of the drug groups with different concentrations was significantly reduced and the cell proliferation activity was significantly reduced compared to the blank control group. The results show that the carboline derivative can effectively inhibit the growth and proliferation of thyroid cancer TP-1 cells, and the higher the action concentration is, the stronger the inhibition effect is.

TABLE 1 measurement results of cell proliferation Activity

Group of	OD570 value	Cell proliferation Activity (%)
			Blank control group	0.708±0.023	100
Carboline derivative group (100 n)M)	0.594±0.020	83.90
			Carboline derivative group (200nM)	0.472±0.021	66.67
Carboline derivative group (500nM)	0.366±0.018	51.69

2. Results of measurement of cell migration Activity

Fig. 2 is a set of representative migration photographing results, and the scratch distance of the carboline derivative group is significantly higher than that of the control group, which illustrates that the migration activity of the thyroid cancer TP-1 cells in the carboline derivative group is significantly reduced.

The experiments show that the carboline derivative can inhibit the growth and proliferation of thyroid cancer TP-1 cells and can also inhibit the migration activity of the thyroid cancer TP-1 cells, so that the carboline derivative can be developed into an anti-tumor medicament for inhibiting the growth and/or the metastasis of the thyroid cancer.

The foregoing embodiments are provided to illustrate the present invention more fully, but those skilled in the art will appreciate that the scope of the present invention should not be limited to the specific embodiments described above.