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Application of nuclear export protein inhibitor kpt-335 and its composition in antitumor drugs

A KPT-335, protein inhibitor technology, applied in the field of biomedicine to achieve good inhibitory effect, improved curative effect, and low toxicity

Active Publication Date: 2022-04-19
SHENZHEN PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no relevant research report on the combination of nuclear export inhibitors and IRE1 inhibitors for anti-tumor

Method used

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  • Application of nuclear export protein inhibitor kpt-335 and its composition in antitumor drugs
  • Application of nuclear export protein inhibitor kpt-335 and its composition in antitumor drugs
  • Application of nuclear export protein inhibitor kpt-335 and its composition in antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Embodiment 1, the effect of KPT-335 single use on the proliferation of tumor cells and normal cells

[0026] Esophageal cancer cell lines KYSE30, Eca-109, KYSE450, KYSE510, breast cancer cell line BT549, lung cancer cell line PC-9, colorectal cancer cell lines HCT8, HCT116 and normal vascular endothelial cells HUVEC were used at 3000-6000 per well The number of cells was inoculated into a 96-well plate. After the cells adhered to the wall, the blank control group and different doses of KPT-335 experimental groups (0-10 μM) were added; after 48 hours of culture, 10 μL of CCK-8 solution was added to each well, and the culture was continued for 1 hour , read the OD value (wavelength 450nm) on a microplate reader, read the absorbance value of each well, and calculate the cell viability. According to the formula of cell survival rate (%)=(OD experimental group-OD blank) / (OD control group-OD blank)×100%, the cell survival rate is calculated, and the results are detailed in f...

Embodiment 2

[0030] Embodiment 2, the effect of KPT-335 alone on the migration of esophageal cancer cells

[0031] Esophageal cancer cell lines KYSE30 and KYSE450 were inoculated into 96-well plates at the number of 12,000 cells per well. After the cells adhered to the wall, they were synchronized for 12 hours, scratched with a scratch instrument, washed twice with PBS, and replaced with 2% Fetal bovine serum medium, take pictures, this time is 0h, then add the blank control group and the KPT-335 experimental group with doses of 0, 5, 2.5, 1.25, 0.625, 0.31125 μM respectively, take pictures after 24 hours of culture, measure Width, calculate mobility. According to cell migration ratio=width (experimental group 0h-experimental group 24h) / width (blank group 0h-blank group 24h) × 100%, the results are shown in Table 2 and figure 2 .

[0032] Table 2 The results of each cell migration rate measurement

[0033]

[0034]

[0035] From Table 2 and figure 2It can be seen that 5 μM KPT-...

Embodiment 3

[0036] Embodiment 3, the effect of KPT-335 alone on the apoptosis protein of esophageal cancer cells

[0037] First, the esophageal cancer cells KYSE30 and KYSE450 were divided into 3.5×10 5 cells at a density of 6 wells. After the cells adhered to the wall, they were treated with different concentrations for 24 hours, and the total protein of the cells in each group was collected respectively. After SDS electrophoresis, the protein was transferred to a PVDF membrane, blocked with 5% skimmed milk powder at room temperature for 1 hour, incubated with the primary antibody corresponding to the protein to be detected, and incubated overnight at 4°C. After 24 hours, the primary antibody was recovered, washed three times with TBST for 5 minutes each time, and then incubated with the secondary antibody for 1 hour at room temperature. After washing with TBST for 3 times for 5 min each time, ECL imaging was performed to detect the expression of apoptosis pathway-related proteins PARP...

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Abstract

The invention belongs to the field of biomedicine, and specifically relates to the application of nuclear export protein inhibitor KPT-335 and its composition in anti-tumor. Gastric cancer and liver cancer cells have significant therapeutic effects, and at the same time have less toxicity to normal cells. The nuclear export protein inhibitor KPT-335 of the present invention has a significant inhibitory effect on the proliferation and migration of esophageal cancer cells, and can significantly increase Cleaved-PARP and significantly reduce the expression of XPO1 to promote apoptosis. The composition of KPT-335 and IRE1 inhibitor contained in the present invention improves the bioavailability of the drug, and at the same time, can produce a synergistic effect on the drug effect, which is obviously better than single drug use.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of a nuclear export protein inhibitor and a composition thereof in antitumor drugs. Background technique [0002] Cancer, the second leading cause of death worldwide, is characterized by uncontrolled cell proliferation and can also produce abnormal cell clumps, or tumors. The primary tumor grows due to new blood vessel formation and, over time, spreads to other body parts, causing metastasis and eventually death. Cancer is caused by damage or mutation of a cell's genetic material due to environmental or genetic factors. Surgery and radiation therapy are the main treatments used for localized and non-metastatic cancers, while chemotherapy with anticancer drugs is currently the option for metastatic cancers. Traditional chemotherapeutic drugs have the disadvantages of low selectivity, many adverse reactions, and easy drug resistance, which have been difficul...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/454A61P35/00
CPCA61K31/454A61P35/00
Inventor 王晓黄维欧玲王绍祥谢守霞
Owner SHENZHEN PEOPLES HOSPITAL
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