Pharmaceutical composition containing PI3K inhibitor and application of pharmaceutical composition

A composition and inhibitor technology, applied in the field of biomedicine, to achieve the effects of improved curative effect, significant therapeutic effect, and low toxicity

Pending Publication Date: 2021-04-13
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 combined use of PI3K inhibitors and HSP inhibitors for anti-tumor drug resistance

Method used

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  • Pharmaceutical composition containing PI3K inhibitor and application of pharmaceutical composition
  • Pharmaceutical composition containing PI3K inhibitor and application of pharmaceutical composition
  • Pharmaceutical composition containing PI3K inhibitor and application of pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1, the effect of LY294002 acting alone on the migration of esophageal cancer cells

[0027] 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 LY294002 experimental group with doses of 0, 30, 15, 7.5, 3.25 μM respectively, take pictures after 24 hours of culture, measure the width, and calculate the migration Rate. According to cell migration ratio=width (experimental group 0h-experimental group 24h) / width (blank group 0h-blank group 24h)ⅹ100%, the results are detailed in figure 1 and Table 1.

[0028] Table 1 The results of each cell migration rate measurement

[0029]

[0030] From Table 1 and figure 1 It can be seen that LY294002 ...

Embodiment 2

[0031] Example 2, the combined effect of LY294002 and SNX-2112 on tumor cells and normal cells

[0032] KYSE30 esophageal cancer cell line, ECA-109 esophageal cancer cell line, cisplatin-resistant ECA-109 esophageal cancer cell line, A549 lung cancer cell line, HepG2 liver cancer cell line and HUVEC normal vascular endothelial cells were used at 3000-6000 cells per well The number was inoculated into 96-well plates, and after the cells adhered to the wall, the cells were divided into control group, LY294002 single drug group, SNX-2112 single drug group and LY294002 and SNX-2112 drug combination group; after 48 hours of culture, each well was added 10 μL of CCK-8 solution, continue to culture for 1 h, read the OD value (wavelength 450 nm) on a microplate reader, read the absorbance value of each well, and calculate the cell survival rate. According to the formula of cell survival rate (%)=(OD experimental group-OD blank) / (OD control group-OD blank)×100%, calculate the cell surv...

Embodiment 3

[0034] Example 3. The combined effect of LY294002 and SNX-2112 on the migration of drug-resistant esophageal cancer cells

[0035] Human cisplatin-resistant ECA-109 esophageal cancer cells were inoculated into a 96-well plate at a rate of 12,000 cells per well. After the cells adhered to the wall, they were synchronized for 12 hours, scratched with a scratch instrument, and washed twice with PBS. Change the medium containing 2% fetal bovine serum and take pictures. At 0h, divide the cells into control group, LY294002 single-drug group, SNX-2112 single-drug group and LY294002 and SNX-2112 drug combination group. culture medium or drug solution, take pictures after 24 hours of culture, measure the width, and calculate the mobility. According to cell migration ratio=width (experimental group 0h-experimental group 24h) / width (blank group 0h-blank group 24h)×100%, the results are detailed in image 3 .

[0036] From image 3 It can be seen that, compared with the control group and...

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PUM

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Abstract

The invention belongs to the field of biological medicine, and particularly relates to a pharmaceutical composition containing a PI3K inhibitor and application of the pharmaceutical composition. The composition comprises an effective quantity of the PI3K inhibitor, an effective quantity of an HSP90 inhibitor and a pharmaceutically acceptable carrier. The pharmaceutical composition containing the PI3K inhibitor has a remarkable treatment effect on esophageal cancer cells, lung cancer cells, gastric cancer cells and liver cancer cells, is low in toxicity to normal cells, has a remarkable inhibition effect on proliferation and migration of the esophageal cancer cells, and can remarkably improve expression of Cleaved-PARP and promote apoptosis at the same time. According to the pharmaceutical composition containing the PI3K inhibitor, the bioavailability of drugs is improved, the drug effect can generate a synergistic interaction effect, and the drug resistance treatment effect on tumors is obviously superior to that of a single drug.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a pharmaceutical composition containing a PI3K inhibitor and an application thereof. Background technique [0002] The global cancer situation is getting worse and worse, and the number of cancer deaths will increase from 6 million to 10 million per year. With the improvement of living standards and changes in dietary structure, the incidence of esophageal cancer is increasing year by year; primary liver cancer is one of the most common malignant tumors in humans; lung cancer is a common malignant tumor, divided into cell lung cancer and non-small cell lung cancer. cell lung cancer. Although the treatment of these cancers is mainly based on surgery, since early patients generally have no obvious symptoms, many of the cancer patients diagnosed for the first time are already in the middle and advanced stages, so non-surgical treatment (such as chemotherapy) plays a very impo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/5377A61K31/416A61P35/00
CPCA61K45/06A61K31/5377A61K31/416A61P35/00A61K2300/00
Inventor 王晓欧玲王绍祥谢守霞黄维唐倩常港刘凯
Owner SHENZHEN PEOPLES HOSPITAL
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