Promoter for reducing malignant phenotypes of pancreatic cancer cells, pharmaceutical composition and application thereof
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A technology of pancreatic cancer cells and promoters, applied in the field of promoters and pharmaceutical compositions that reduce the malignant phenotype of pancreatic cancer cells, can solve the problems of less than 10% remission rate and increased side effects
Pending Publication Date: 2022-05-31
XINXIANG MEDICAL UNIV
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At present, gemcitabine is the first-line drug for the treatment of pancreatic cancer, but the response rate of its single drug is less than 10%. ) Quadruple chemotherapeutic drugs have slightly improved curative effect but greatly increased side effects. Its limited curative effect and unavoidable toxic and side effects prompt us to look for new drug targets in order to improve the therapeutic effect and improve the prognosis of patients.
However, the role and possible mechanism of BH4 in pancreatic cancer cells have not been reported yet.
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Embodiment 1
[0028] Embodiment 1 Experimental grouping and model construction
[0029] 1.1 Cell culture:
[0030] PANC-1 cells, using DMEM high glucose medium, 37°C, 5% CO 2 Cultured in a constant temperature incubator, passaged once every 2-3 days, and the cells cultured to the logarithmic growth phase were used for experiments;
[0031] BxPC-3 cells, using RPMI-1640 medium (containing 10% FBS, 100U / L penicillin and 100μg / mL streptomycin), 37 ° C, 5% CO 2 Cultured in a constant temperature incubator, passaged once every 2-3 days, and the cells cultured to the logarithmic growth phase were used for experiments;
[0032] 1.2 Experimental grouping and cell culture methods:
[0033] 1.2.1 Effect of cell viability and apoptosis
[0034] The PANC-1 and BxPC-3 cells in the logarithmic growth phase were inoculated in 96 wells and cultured for 12 hours. Each cell was divided into the control group and the experimental group. The control group and the experimental group were inoculated in 10 we...
Embodiment 2
[0039] Various performance tests of each control group and experimental group cells of embodiment 2
[0040] 2.1 Using CCK-8 assay to detect the effect of BH4 on the viability of PANC-1 cells and BxPC-3 cells
[0041] After the cell culture was carried out according to the experimental grouping and cell culture method described in Example 1, 100 μL CCK-8 was added to each well of the control group and the experimental group, and after culturing at 37° C. for 2 hours, the OD value was measured at 450 nm with a microplate reader. The results are shown in the following table 1 shows:
[0042] Table 1 The effect of tetrahydrobiopterin on the viability of PANC-1 cells and BxPC-3 cells
[0043] group PANC-1 cells (OD value) BxPC-3 cells (OD value) control group 0.974±0.023 0.913±0.010 2μMBH4 0.848±0.037 0.892±0.013 4μMBH4 0.811±0.025 0.853±0.022 8μMBH4 0.623±0.018* 0.536±0.024* 12 μM MBH4 0.512±0.021** 0.507±0.026*
[0044] * P...
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Abstract
The invention relates to the technical field of tumor medicine research and development, in particular to an accelerant for reducing malignant phenotypes of pancreatic cancer cells, a pharmaceutical composition and application of the accelerant and the pharmaceutical composition. According to the invention, tetrahydrobiopterin acts on PANC-1 and BxPC-3 cells, along with the increase of the concentration of tetrahydrobiopterin, the activity of cancer cells is gradually reduced, the apoptosis number of cancer cells is gradually increased, and the apoptosis rate is increased; the tetrahydrobiopterin can reduce the healing area of the two cancer cells, promote the expression of E-cadherin in the cancer cells, inhibit the expression of N-cadherin, inhibit the epithelial-mesenchymal transition of pancreatic cancer cells and reduce the malignant phenotype of the cancer cells, thereby reducing the migration and invasion ability of the cancer cells. It is indicated that the BH4 bioactive activator can inhibit pancreatic cancer cell proliferation activity and cell migration ability, promote cell apoptosis and inhibit cancer cell epithelial-mesenchymal transition, so that the malignant phenotype of cancer cells is reduced, and the BH4 bioactive activator can be used as a treatment target of pancreatic cancer.
Description
technical field [0001] The invention relates to the technical field of research and development of tumor medicine, in particular to an accelerator for reducing the malignant phenotype of pancreatic cancer cells, a pharmaceutical composition and uses thereof. Background technique [0002] Pancreatic cancer is a digestive system tumor with an insidious onset and a high degree of malignancy. It is the fourth leading cause of cancer-related death, and the mortality rate of patients is slowly increasing at a rate of 1% per year. The overall 5-year survival rate of patients is only 10%. %, the 5-year survival rate of advanced patients is less than 3%. The reasons for such a low survival rate mainly include the high degree of malignancy, insidious onset, no typical symptoms, low resection rate, and high recurrence rate. Due to the insidious onset of pancreatic cancer and the difficulty of early diagnosis, most patients are already at an advanced stage when they see a doctor and los...
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