Application of naphthoquinone compound in preparing drug for treating or preventing pancreatic cancers

A compound, pancreatic cancer technology, applied in drug combination, digestive system, antitumor drugs, etc., can solve problems such as pancreatic cancer cell cycle arrest

Inactive Publication Date: 2019-01-04
天津市中西医结合医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, more and more people are focusing on the anticancer activity of plumbagin in different tumors, including breast cancer, pancreatic cancer, lung cancer and prostate cancer. Through PI3K / AKT / mTOR, AMPK phosphorylation and reactive oxygen species, plumbagin can inhibit the proliferation of pancreatic cancer cells, mediate apoptosis and autophagy, and induce pancreatic cancer cell cycle arrest. Research on the tumor immune microenvironment has not been reported yet

Method used

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  • Application of naphthoquinone compound in preparing drug for treating or preventing pancreatic cancers
  • Application of naphthoquinone compound in preparing drug for treating or preventing pancreatic cancers
  • Application of naphthoquinone compound in preparing drug for treating or preventing pancreatic cancers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1 plumbagin inhibits the differentiation of PBMCs to MDSCs in vitro

[0064] 1.1 Objects and methods

[0065] 1.1.1 Reagent preparation

[0066] (1) Preparation of 0.0lM PBS (PH 7.2‐7.4):

[0067] Weigh Na with a balance 2 HPO 4 1.54g, KH 2 PO 4 0.2g, NaCl 8.0g, KCl 0.2g, add the reagents into 800mL double-distilled water, stir until dissolved, then adjust the volume to 1L, adjust the pH value to 7.2-7.4. Autoclave for future use, and store at 4°C for future use.

[0068] (2) Preparation of antibody diluent:

[0069] Weigh 0.2mg BSA with a balance, pipette 1mL 10% NaN 3 And add 80mL of PBS, stir until dissolved, and then dilute to 100mL. Store in a 4°C refrigerator for later use.

[0070] (3) Staining buffer (Staining buffer, SB) preparation:

[0071] Pipette 1mL of FBS and 10% NaN respectively 3 And add 80mL of PBS, stir and mix well and then dilute to 100mL. Store in a 4°C refrigerator for later use.

[0072] (4) Preparation of complete medium ...

Embodiment 2

[0202] Example 2 plumbagin inhibits the growth of pancreatic cancer in mice

[0203] 2.1 Objects and methods

[0204] 2.1.1 Reagent preparation

[0205] (1) Dissolving plumbagin

[0206] Plumbagin was purchased from Bailingwei Technology Co., Ltd. and stored at room temperature.

[0207] Preparation of plumbagin stock solution: Weigh 10 mg plumbagin powder and dissolve it in 1062.8 μL dimethyl sulfoxide (DMSO), vortex until completely dissolved. tube, stored at -20°C.

[0208] (2) Preparation of 10% bovine serum albumin (10% BSA):

[0209] Use a balance to weigh 1g of BSA and add it to 10mL of PBS, and vortex until it is completely dissolved. 10% bovine serum albumin (10% BSA) needs to be stored in a refrigerator at 4°C.

[0210] (3) Preparation of tumor tissue digestion solution (50×):

[0211] Weigh 15 mg of collagenase IV, 15 mg of deoxyribonucleotidase I and 15 mg of hyaluronidase into 6 mL of PBS, vortex fully until completely dissolved, filter with a 0.22 μm filte...

Embodiment 3

[0283] Example 3 Research on the Mechanism of Plumbagin Inhibiting the Differentiation of MDSCs

[0284] 3.1 Objects and methods

[0285] 3.1.2 Reagent preparation

[0286] (1) Preparation of 0.0l M PBS (PH 7.2‐7.4):

[0287] Weigh Na with a balance 2 HPO 4 1.54g, KH 2 PO 4 0.2g, NaCl 8.0g, KCl 0.2g, add the reagents into 800mL double-distilled water, stir until dissolved, then adjust the volume to 1L, adjust the pH value to 7.2-7.4. Autoclave for future use, and store at 4°C for future use.

[0288] (2) Preparation of Running buffer:

[0289] Weigh 14.4g of glycine, 3.02g of Tris-base, and 1.0g of SDS with a balance, add the reagents into 800mL of double-distilled water, stir until dissolved, and then dilute to 1L.

[0290] (3) Preparation of Trans buffer:

[0291] Weigh 14.4g of glycine, 3.02g of Tris-base, and 1.0g of SDS with a balance, add the reagents into 700mL of double-distilled water, stir until dissolved, add 200mL of methanol, stir well and then dilute t...

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PUM

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Abstract

Starting from clinics, it is found through repeated study at the animal level that by inhibiting differentiation of MDSCs, plumbagin can inhibit the inhibiting effect of MDSCs on effector T cells, promote the infiltration of anti-tumor immune cell sub-populations in a tumor micro-environment and inhibit recruitment of immunity inhibitive cells MDSCs towards tumor tissue to achieve the anti-pancreatic-cancer effect. Plumbagin can directly act on MDSCs or indirectly inhibit differentiation and functions of MDSCs by inhibiting expression of CCL2, IL-6 and other relevant inflammatory cytokines. These results show that plumbagin may be a new drug for treating pancreatic cancers; meanwhile, a new scientific basis is provided for immunological therapy of the pancreatic cancers.

Description

technical field [0001] The invention belongs to the field of biotechnology, and specifically relates to the application of naphthoquinone compounds in the preparation of drugs for treating or preventing pancreatic cancer. Background technique [0002] Pancreatic cancer is a highly fatal tumor with increasing morbidity and mortality year by year. It is difficult to be detected in the early stage of the disease and has an unusual tendency to metastasize. Coupled with its resistance to traditional chemotherapy and radiotherapy, the prognosis of pancreatic cancer is poor. Twenty-five percent of pancreatic cancer patients survive one year after diagnosis, and only 5 percent survive five years. Pancreatic cancer is the sixth leading cause of cancer death in China. Currently, pancreatic cancer treatment strategies include surgical resection, chemotherapy, radiotherapy, immunotherapy, and vaccines. For pancreatic cancer patients, surgical resection is still the main method of trea...

Claims

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Application Information

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IPC IPC(8): A61K31/122A61P1/18A61P35/00
CPCA61K31/122A61P1/18A61P35/00
Inventor 张琦张荣信管志玉程英楠
Owner 天津市中西医结合医院
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