CN114588165A - Application of gambogic acid and oxaliplatin in preparation of pancreatic cancer treatment drug - Google Patents

Application of gambogic acid and oxaliplatin in preparation of pancreatic cancer treatment drug Download PDF

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Publication number
CN114588165A
CN114588165A CN202210277032.0A CN202210277032A CN114588165A CN 114588165 A CN114588165 A CN 114588165A CN 202210277032 A CN202210277032 A CN 202210277032A CN 114588165 A CN114588165 A CN 114588165A
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oxaliplatin
gambogic acid
pancreatic cancer
pac
preparation
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杨林
郭青龙
周煜新
郭滨
郭永健
葛展虹
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Nanjing Qinkang Pharmaceutical Technology Co ltd
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Nanjing Qinkang Pharmaceutical Technology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/555Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

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  • Pharmacology & Pharmacy (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
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  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention discloses application of gambogic acid and oxaliplatin in preparation of a pancreatic cancer treatment drug, and belongs to the technical field of biological medicines. The invention discovers that Gambogic Acid (GA) extracted from a natural product gamboge and Oxaliplatin (OXA) serving as a novel platinum anticancer drug can obviously inhibit the growth of pancreatic cancer (PaC) cells. MTT experiments verify that gambogic acid with lower concentration and a novel platinum anticancer drug oxaliplatin can play a synergistic anti-PaC effect, and the application potential of the combined administration mode in the treatment of PaC is prompted.

Description

Application of gambogic acid and oxaliplatin in preparation of pancreatic cancer treatment drug
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of gambogic acid and oxaliplatin in preparation of a pancreatic cancer treatment medicine.
Background
Gambogic Acid (GA) is one of the main components separated from Garcinia cambogia, has strong antitumor effect, is effective at low concentration, and has good safety and large therapeutic index. Oxaliplatin is a novel platinum anticancer drug, and shows good antitumor effect in pancreatic cancer and various tumor models. Gemcitabine has become the standard adjuvant treatment for pancreatic cancer for the past 10 years, and in recent years FOLFIRINOX regimens containing oxaliplatin have been used as the first line treatment for metastatic pancreatic cancer, greatly extending patient survival. The effect of the FOLFIRINOX regimen in pancreatic cancer has been demonstrated to be significantly superior to gemcitabine monotherapy. The research researches the combined effect of the gambogic acid and the oxaliplatin and provides reference for clinical treatment of pancreatic cancer and treatment schemes for the pancreatic cancer.
Disclosure of Invention
The invention aims to provide application of gambogic acid and oxaliplatin in preparation of a pancreatic cancer treatment drug. The invention discovers that Gambogic Acid (GA) extracted from natural product gamboge and a novel platinum anticancer drug Oxaliplatin (OXA) can obviously inhibit the growth of pancreatic cancer (PaC) cells. MTT experiments verify that gambogic acid with lower concentration and a novel platinum anticancer drug oxaliplatin can play a synergistic anti-PaC effect, and the application potential of the combined administration mode in the treatment of PaC is prompted.
Drawings
FIG. 1 shows the effect of gambogic acid and oxaliplatin on the proliferation of pancreatic cancer cell line BXPC 3.
Detailed Description
The invention is described in further detail below with reference to the figures and the specific examples, which should not be construed as limiting the invention. Modifications or substitutions to methods, steps or conditions of the present invention may be made without departing from the spirit and scope of the invention. The experimental methods and reagents of the formulations not specified in the examples are in accordance with the conventional conditions in the art.
Example 1
1. Experimental Material
(1) Gambogic acid (C)33H44O8Molecular weight: 628.7512) was supplied by university of Chinese pharmacy as yellow powder with 95% purity, and the drug powder was made up to 0.01M stock solution with dimethyl sulfoxide (DMSO) before use and stored at-80 ℃. Oxaliplatin powder was purchased from CSNpharm reagent, stored at-20 ℃ in the dark, prepared as a 0.005M stock solution with sterile water before use, stored at-80 ℃ and prepared to the desired concentration with RPMI-1640 medium containing 10% fetal bovine serum just before use.
(2) Cell culture reagent
Culture solution: RPMI-1640 medium, purchased from GIBCO, USA. Dissolving 10.39 g of RPMI-1640 powder in 1000 mL of sterilized triple distilled water, and adding 2.0 g of NaHCO3Adjusting pH to 7.0 with 1M hydrochloric acid, filtering with cylindrical filter, sterilizing, packaging, and storing in refrigerator at 4 deg.C. Before use, 100U/mL penicillin and 100U/mL streptomycin are added.
② fetal bovine serum: product of GIBCO, usa. Inactivating in 56 deg.C water bath for 30 min, subpackaging, and storing in-20 deg.C low temperature refrigerator.
(iii) PBS buffer: weighing 8.0 g of NaCl, 0.20 g of KCl and Na2HPO4·H2O 1.56 g、KH2PO4.2.0 g, dissolved in 1000 mL of triple distilled water, autoclaved, and stored in a refrigerator at 4 ℃.
(3) Cell growth activity inhibition detection related reagent
MTT powder was purchased from Sigma-Aldrich.
(4) Cell line
Human PaC cell line BXPC3 was purchased from Shanghai national academy of sciences. Cells were cultured in RPMI1640 medium containing 100U/mL penicillin, 100 mg/mL streptomycin and 10% fetal bovine serum.
2. Experimental methods
MTT assay
MTT solution can be reduced into blue-violet crystal formazan by mitochondrial dehydrogenase in living cells, and the DMSO can dissolve the formazan, and the color shade of the formed solution is in direct proportion to the cell activity, so that the cell activity can be detected. Culturing cells in a 96-well enzyme label plate according to a proper cell density, wherein the volume of the cells in each well is 100 muL, when the cells are attached to the wall and the fusion degree reaches 50%, absorbing a culture medium, and adding 100 muL of gambogic acid and oxaliplatin (100, 120, 140, 160, 180, 200, 220, 240, 260, 280 muM) with the concentration of 0 or 0.5 muM; continuously placing the cells to which the medicines are given in an incubator for culturing for 24 hours, and adding 20 muL of MTT solution into each hole; and after continuously incubating for 4 h, removing the supernatant, adding 100 mu L DMSO into each hole, placing the hole in a micro oscillator for oscillation, and detecting the absorbance of the crystal by using a wavelength of 570 nm after the crystal is completely dissolved. And (3) after the detected light absorption value is finished, calculating the growth inhibition rate of the drug to the cells according to the following formula:
Figure DEST_PATH_IMAGE001
3. results of the experiment
The inhibition effect of the natural product gambogic acid combined with oxaliplatin on the growth of the PaC cell line BXPC3 at the 24 h time point was determined by MTT experiment. As shown in figure 1, the combination of gambogic acid and oxaliplatin (GA-0.5) can significantly inhibit the growth of PaC cells BXPC3 cells compared to the oxaliplatin single group (GA-0), and the results preliminarily confirm the anti-PaC effect of gambogic acid in combination with chemotherapeutic drugs.

Claims (4)

1. Application of gambogic acid and oxaliplatin in preparation of pancreatic cancer treatment medicines.
2. Use according to claim 1, characterized in that: the concentration ratio of gambogic acid to oxaliplatin is 0.5: 100-280.
3. A pancreatic cancer treatment drug characterized by: the active ingredients of the medicine are gambogic acid and oxaliplatin.
4. The medicament of claim 3, wherein: the concentration ratio of gambogic acid to oxaliplatin is 0.5: 100-280.
CN202210277032.0A 2022-03-21 2022-03-21 Application of gambogic acid and oxaliplatin in preparation of pancreatic cancer treatment drug Pending CN114588165A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210277032.0A CN114588165A (en) 2022-03-21 2022-03-21 Application of gambogic acid and oxaliplatin in preparation of pancreatic cancer treatment drug

Applications Claiming Priority (1)

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CN202210277032.0A CN114588165A (en) 2022-03-21 2022-03-21 Application of gambogic acid and oxaliplatin in preparation of pancreatic cancer treatment drug

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101361732A (en) * 2007-08-09 2009-02-11 江苏康缘药业股份有限公司 Medicinal preparation containing garcinia acid and use thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101361732A (en) * 2007-08-09 2009-02-11 江苏康缘药业股份有限公司 Medicinal preparation containing garcinia acid and use thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
刘静冰等: "藤黄酸抗胰腺癌作用的实验研究", 《临床肿瘤学杂志》, vol. 10, no. 3, pages 274 - 277 *

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