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Novel FGF analogue for treating breast cancer and application thereof

An analogue, breast cancer technology, applied in the field of medicine, can solve the problems of weak targeting and many side effects, and achieve the effects of alleviating the occurrence and development, inhibiting the generation and metastasis, and reducing the size

Pending Publication Date: 2022-01-11
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the currently developed drugs are all small molecule inhibitors with weak targeting and more side effects, while bioprotein drugs absorb quickly and have strong targeting

Method used

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  • Novel FGF analogue for treating breast cancer and application thereof
  • Novel FGF analogue for treating breast cancer and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1: Construction, expression and purification of recombinant proteins

[0030] (1) Construction of FGF21 protein expression vector

[0031] According to the computer simulation replacement and Escherichia coli codon preference, a novel FGF21 gene was designed, and its nucleotide sequences were respectively as shown in FGF21-1 (nucleotide sequence as SEQ ID NO.4) and FGF21-2 (nucleosides) in the sequence listing. The acid sequence is shown in SEQ ID NO.5), FGF21-3 (the nucleotide sequence is shown in SEQ ID NO.6). These three genes were sent to Shanghai Jierui Biological Co., Ltd. for synthesis, and NdeI and BamHI restriction sites were designed at both ends of each gene. The three synthetic vectors containing the respective target gene fragments and pET30a(+) were double-digested with NdeI and BamHI respectively, and after the digestion was completed, the required target fragments were recovered from the gel. The four target fragments were ligated with the prok...

Embodiment 2

[0034] Example 2: Effect of FGF21 on growth rate of human breast cancer xenografts

[0035] The FGF21 protein whose amino acid sequence is shown in SEQ ID NO.1 was prepared according to the method of Example 1.

[0036] Human breast cancer cell MDA-MB-231 cells were inoculated subcutaneously in 6-week-old male nude mice at 1×106 cells / only until the tumor grew to 200mm 3 Randomly divided into four groups:

[0037] ①Normal saline group: inject equal volume of normal saline; ②Low-dose group: inject 1 mg / kg FGF21; ③Middle-dose group: inject 5 mg / kg FGF21; ④High-dose group: inject 10 mg / kg FGF21.

[0038] Inject once a day for 15 consecutive days. Tumor volume was monitored daily, mice were sacrificed three weeks later, and tumor weight was measured.

[0039] The results showed that three different doses of FGF21 could inhibit the transplanted tumor volume and final tumor weight in a dose-dependent manner. After high-dose FGF21 (10mg / kg) injection, it can completely inhibit tumo...

Embodiment 3

[0040] Example 3: Effect of FGF21 on MMTV-PYVT spontaneous mouse breast cancer

[0041] The FGF21 protein whose amino acid sequence is shown in SEQ ID NO.1 was prepared according to the method of Example 1.

[0042] The positive mice were identified as positive mice after birth and were divided into normal saline group and FGF21 injection group at the 6th week. After 1 week and 8 weeks, the number and mass of tumors in the normal saline group and the FGF21 injection group were measured respectively.

[0043] The result is as figure 2 As shown in A, the average number of tumor foci can be reduced from 8 to 3.8 after injection of FGF21, figure 2 B shows the tumor weight of the FGF21 treatment group and the control group, the tumor weight in the treatment group is only 1 / 3 of the control group.

[0044] The inventor also tried to study the effect of the fusion protein of FGF21 protein shown in SEQ ID NO. It has a comparable effect with the FGF21 protein shown in SEQ ID NO.1...

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Abstract

The invention discloses a novel FGF analogue for treating breast cancer and application thereof, and belongs to the technical field of medicines. A FGF21 protein is a secretory protein consisting of about 210 amino acids, the FGF21 is found to have the effect of treating breast cancer for the first time, and cytological experiments and animal experiments prove that the FGF21 can inhibit proliferation, invasion and migration of breast cancer cell lines; and the size of a tumor focus can be obviously reduced in a mouse model. The breast cancer treatment medicine prepared by taking the FGF21 as an active substance has the effects of being good in safety, long in medicine effect lasting time, capable of protecting organs from being damaged and capable of improving lipid metabolism disorder.

Description

technical field [0001] The invention relates to a novel FGF analogue for treating breast cancer and its application, in particular to the application of human FGF21 analogue in the preparation of drugs for treating breast cancer, and belongs to the field of medical technology. Background technique [0002] Breast cancer is one of the most common clinical malignant tumors. According to the latest data from the International Agency for Research on Cancer (IARC) survey in 2018, the incidence rate of breast cancer in women's cancers in the world is 24.2%, ranking first among women's cancers. 52.9% occurred in developing countries. [0003] At present, the treatment of breast cancer is mainly based on radical surgery, chemotherapy, radiotherapy, traditional Chinese medicine treatment and biological therapy as its auxiliary treatment means. Approximately two-thirds of patients diagnosed for the first time underwent radical surgery, and more than half of these patients developed r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/50C12N15/12C12N15/70C12N1/21A61K38/18A61P35/00C12Q1/6886C12R1/19
CPCC07K14/50C12N15/70A61P35/00C12Q1/6886A61K38/00C12Q2600/136
Inventor 朱升龙陈永泉王振
Owner JIANGNAN UNIV
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