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Tumor radiosensitizer containing eEF2K inhibitor

A tumor radiation and sensitizer technology, applied in the clinical field, can solve the problems of increasing the efficacy of cancer radiotherapy, target-specific toxicity, low radiation dose, etc., and achieve the effect of reducing complications, reducing impact, and low radiation dose.

Active Publication Date: 2016-07-27
JIANGSU PROVINCE HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Researchers have long hoped to develop radiosensitizers that could increase the efficacy of cancer radiation therapy with lower radiation doses, potential target specificity, and clinically acceptable toxicity

Method used

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  • Tumor radiosensitizer containing eEF2K inhibitor
  • Tumor radiosensitizer containing eEF2K inhibitor
  • Tumor radiosensitizer containing eEF2K inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1W

[0024] Example 1 WesternBlot detects the effect of NH-125 on breast cancer cell eEF2K targeting inhibition

[0025] Two types of breast cancer cells MCF-7 and MDA-MB-231 were pretreated with different concentrations of NH-125 for 24 hours and then lysed with RIPA containing 10% PMSF, shaken on ice for 15 minutes, collected, centrifuged at 12,000 rpm for 15 minutes, protein BCA After the kit is quantified, add 5X loadingbuffer and cook for 5 minutes to denature. Electrophoresis with 10% SDS-PAGE gel at 80V for one hour, then switch to 120V for another hour, PVDF membrane 250mA for 100 minutes, 5% milk blocking for 1 hour, primary antibody 4℃ incubation overnight, TBST wash 3 times, 15 minutes each time Incubate the secondary antibody for 1 hour, wash three times with TBST, 15 minutes each time, and develop exposure.

[0026] The result is figure 1 Shown from figure 1 It can be seen that as the concentration of NH125 increases, eEF2K expression is significantly inhibited.

Embodiment 2C

[0027] Example 2 CCK8 experiment to detect the effect of NH-125 on breast cancer cell proliferation:

[0028] Breast cancer cells MCF-7 and MDA-MB-231 were evenly spread in a 96-well plate overnight at a density of 5000 cells / well. The next day, they were treated with different concentrations of NH-125 for 24h and 48h, and then 10% was added to each well. Incubate in CCK at 837°C for 1.5h, then measure the OD value with a spectrophotometer at 450nm wavelength to calculate the cell proliferation.

[0029] The result is figure 2 Shown from figure 2 It can be seen that as the dose of NH-125 increases, cell viability decreases significantly.

Embodiment 3

[0030] Example 3 The clone formation experiment detects the effect of NH-125 on the sensitivity of breast cancer cells to radiotherapy:

[0031] Breast cancer cells MCF-7 and MDA-MB-231 were planted in six-well plates at different densities. After the cells adhered to the wall, they were treated with 0.1 μM and 0.25 μM for 24 hours and DMSO was used as a control. Then the cells were irradiated with 6MV X-ray at a dose rate of 4.5Gy per minute for 0, 2, 4, 6, 8Gy, and then the cells were cultured for two weeks, then methanol fixed for 30 minutes, washed three times in running water and stained with Giemsa stain For 30 minutes, count the number of clones with more than 50 cells.

[0032] Table 1 The effect of NH-125 on the radiosensitivity of breast cancer cells MCF-7

[0033]

[0034] Table 2 The effect of NH-125 on the radiosensitivity of breast cancer cells MDA-MB-231

[0035] The result is image 3 , Table 1 and Table 2, from image 3 It can be seen from Table 1 and Table 2 that wi...

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Abstract

The invention provides a tumor radiosensitizer containing an eEF2K inhibitor, and particularly relates to the application of NH125 in a breast cancer radiosensitizer.Radiotherapy is conducted after the radiosensitizer is used, and the radiosensitizer has a synergetic effect, low radiation dosage, potential targeting specificity and clinically acceptable toxicity.Radioactive dosage can be reduced, while radiotherapy effect stays the same or even becomes better, influences on surrounding normal tissue are reduced, and then complications caused by radioactive toxin are reduced.

Description

Technical field [0001] The invention belongs to the clinical field, and specifically relates to tumor radiosensitizers containing eEF2K inhibitors, and particularly relates to the application of NH125 in breast cancer radiosensitizers. Background technique [0002] As a method of local treatment of malignant tumors, radiotherapy can preserve normal organs and tissues, so the number of patients treated by this method is increasing rapidly. It is estimated that about two-thirds of cancer patients receive radiotherapy, which involves the application of ionizing radiation as part of the treatment to control or kill malignant cells. Ionizing radiation damages the DNA of exposed tissues and causes cell death. Radiotherapy can treat many types of cancer and can also be used as part of adjuvant therapy to prevent tumor recurrence after surgery. [0003] Different cancers respond differently to radiotherapy. Highly radiation-sensitive cancer cells can be quickly killed by moderate radiat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/55A61K31/4174A61K9/00A61P35/00
CPCA61K9/0019A61K31/4174A61K38/55
Inventor 孙新臣祝鸿程宋洪美陈光宗闵骅王远东戴望舒卢倩
Owner JIANGSU PROVINCE HOSPITAL
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