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Application of phellodendrine or pharmaceutical salt of phellodendrine in tumor treatment aspect

A technology of phellodine and medicinal salt, which is applied in the field of medicine, and can solve problems such as the application of phellodine or its medicinal salt in tumor treatment that has not been reported

Active Publication Date: 2018-07-24
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The prior art has not reported the application of phellodine or its pharmaceutically acceptable salts in tumor therapy

Method used

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  • Application of phellodendrine or pharmaceutical salt of phellodendrine in tumor treatment aspect
  • Application of phellodendrine or pharmaceutical salt of phellodendrine in tumor treatment aspect
  • Application of phellodendrine or pharmaceutical salt of phellodendrine in tumor treatment aspect

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment 1: Phellodendronine anti-tumor spectrum

[0030] 1. Experimental materials

[0031] Phellodendronine hydrochloride was purchased from Chengdu Pufeide Biotechnology Co., Ltd., with a purity of more than 95%.

[0032] Fetal Bovine Serum (FBS) (GIBCO, Invitrogen Corporation, NY, USA); DMEM medium or RPMI-1640 medium or L-15 medium or F12K medium or MEM medium or F-12 medium or IMDM medium (GIBCO, Invitrogen Corporation, NY, USA); penicillin (Sigma, St.Louis, MO, USA); streptomycin (Sigma, St.Louis, MO, USA); trypsin (Gibco, Grand Island , NY, USA); MTT reagent, Biyuntian Institute of Biotechnology.

[0033] Cell lines MCF-7, MDA-MB-231, MDA-MB-468, MDA-MB-453, HCT-116, Lovo, HepG2, Bel7402, SMMC-7721, 95D, NCI-H460, NCI-H446, SGC7901, NCI-N87, PANC-1, Aspc-1, BxPC-3, DU145, PC-3, HL-60, K-562, HUVEC, L02, HEK293, U87, U251 cell line were purchased from American TissueCulture Collection (ATCC, Rockville, MD, USA).

[0034] Experimental instruments include: F...

Embodiment 2

[0051] Example 2: The inhibitory effect of Phellodendronine on KRAS mutant pancreatic cancer

[0052] 1. Experimental materials

[0053] PANC-1 and BxPC-3 cells: obtained from American Type Culture Collection (ATCC).

[0054] Medium A: prepared by adding 10% FBS (EliteBiotech) and 100 units / mL penicillin and 100 μg / mL streptomycin to DMEM medium (GIBCO Company, Grand Island, New York, USA).

[0055] Medium B: 10% dialyzed FBS (PAA Laboratories Ltd., UK) was added to DMEM medium (GIBCO).

[0056] Propranidine hydrochloride (PC) (PubChem CID: 59818): purchased from Chengdu Pufeide Biotechnology Co., Ltd.

[0057] Gemcitabine: purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0058] DMSO: used to prepare compounds from Sigma-Aldrich, St. Louis, Missouri, USA; used for MTT determination from Beijing Dingguo Biotechnology Co., Ltd.

[0059] 3-(4,5-Dimethylthiazole-2)-2,5-diphenyltetrazolium bromide (MTT): from Sigma-Aldrich Company.

[0060] Both crystal viole...

Embodiment 3

[0098] Example 3: Cortexine inhibits pancreatic cancer in vivo

[0099] 1. Experimental materials

[0100] PANC-1 cells obtained from the American Type Culture Collection (ATCC);

[0101] Balb / c nude mice (male, 7 weeks old) were purchased from Nanjing University (Nanjing, China);

[0102] Medium A: Prepared by adding 10% FBS (Elite Biotech) and 100 units / mL penicillin and 100 μg / mL streptomycin to DMEM medium (GIBCO).

[0103] 2. Experimental method

[0104] 1. Xenotransplantation

[0105] Mice acclimated to the environment for a week. Then, PANI-1 cells (2×10 6 cells in DMEM without FBS) and Matrigel (BD biosciences) in equal volumes, with a total volume of 200 μL, were injected subcutaneously into the right side of the mouse. Tumor volumes were checked every two days. When the tumor volume reaches 60-100mm 3 , the mice were randomly divided into 4 groups (n=7 / group): control (vehicle, DMSO, PBS, ip), EIPA (2mg / kg / day, ip) and Phellodendri hydrochloride (30mg / kg / day ...

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Abstract

The invention discloses application of phellodendrine or pharmaceutical salt of the phellodendrine in the tumor treatment aspect. The application finds that the phellodendrine or the pharmaceutical salt of the phellodendrine has the inhibiting effect on breast cancer, colon cancer, liver cancer, gastric cancer, KRAS mutant pancreatic cancer and leukemia, has no obvious inhibition on human normal cells and is hopeful to be developed into low-toxicity anti-tumor medicine, wherein by inhibiting the macropinocytosis effect of KRAS mutant pancreatic cancer cells and reducing the Bcl-2 / Bax expression ratio in the KRAS mutant pancreatic cancer, the phellodendrine or the pharmaceutical salt of the phellodendrine inhibits the multiplication of the KRAS mutant pancreatic cancer and induces the KRASmutant pancreatic cancer to apoptosis. Therefore the phellodendrine or the pharmaceutical salt of the phellodendrine can be developed into a medicine preparation for resisting breast cancer, colon cancer, liver cancer, gastric cancer, KRAS mutant pancreatic cancer or leukemia; the preparation contains the phellodendrine, the pharmaceutical salt of the phellodendrine or prodrug of the phellodendrine, also contains a pharmaceutically acceptable carrier or excipient and is prepared into a pharmaceutically acceptable dosage form.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to the application of phellodine or a medicinal salt thereof in tumor treatment. Background technique [0002] Malignant tumor is a kind of disease that seriously threatens human health, and it is the biggest cause of human death after cardiovascular disease. With the emergence of an aging society and the accelerated pace of life of young people, work pressure increases, the incidence and mortality of malignant tumors increase year by year, and become younger. According to WHO statistics, it is estimated that by 2020, the number of new cancer patients will exceed 15 million each year. If this trend continues, if there is no better treatment, by 2030, as many as 13.2 million people worldwide will die of cancer every year. [0003] Pancreatic cancer is one of the most malignant human tumors, about 90% of which are ductal adenocarcinoma (PDAC) originating from the ductal epithelium. The 5-year...

Claims

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Application Information

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IPC IPC(8): A61K31/4375A61P35/00A61P35/02
CPCA61K31/4375
Inventor 徐晓军李萍朴玛杜李慧霞
Owner CHINA PHARM UNIV
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