CN109223746B - Application of lithospermic acid in reversing drug resistance of ovarian cancer to paclitaxel - Google Patents
Application of lithospermic acid in reversing drug resistance of ovarian cancer to paclitaxel Download PDFInfo
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- CN109223746B CN109223746B CN201811167944.2A CN201811167944A CN109223746B CN 109223746 B CN109223746 B CN 109223746B CN 201811167944 A CN201811167944 A CN 201811167944A CN 109223746 B CN109223746 B CN 109223746B
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- ovarian cancer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The invention discloses an application of alkannic acid in reversing drug resistance of ovarian cancer to paclitaxel. Ovarian cancer is one of the three major malignancies of the female reproductive system, and the survival time of most advanced ovarian cancer patients is no more than 5 years. Clinical treatment of ovarian cancer usually employs tumor cell debulking, followed by platinum and paclitaxel chemotherapy. However, the ovarian cancer cells have high recurrence rate and high death rate due to the resistance of the ovarian cancer cells to the chemotherapeutic drugs, so the ovarian cancer cells become the bottleneck of clinical treatment. The invention discovers that the lac acid, the lac alcohol acid and the cedar acid can enhance the proliferation inhibition effect of Taxol on A2780/Taxol cells to different degrees, improve the sensitivity of the cells on Taxol and can be developed into a medicament for reversing the drug resistance of ovarian cancer to Taxol.
Description
Technical Field
The invention belongs to the field of medicines, and relates to discovery of a medicine for reversing drug resistance of ovarian cancer to paclitaxel.
Background
Ovarian cancer is one of the three major malignancies of the female reproductive system, and the survival time of most advanced ovarian cancer patients is no more than 5 years. Clinical treatment of ovarian cancer usually employs tumor cell debulking, followed by platinum and paclitaxel chemotherapy. However, the ovarian cancer cells have high recurrence rate and high death rate due to the resistance of the ovarian cancer cells to the chemotherapeutic drugs, so the ovarian cancer cells become the bottleneck of clinical treatment.
Disclosure of Invention
The invention aims to provide a medicament for reversing the drug resistance of ovarian cancer to paclitaxel.
The invention is realized by the following technical scheme:
application of Lactaric acid in preparing medicine for reversing drug resistance of ovarian cancer is provided.
Further, the resistance of ovarian cancer to paclitaxel was reversed.
A medicinal preparation for reversing drug resistance of ovarian cancer contains Lactaric acid as active ingredient.
Further, the resistance of ovarian cancer to paclitaxel was reversed.
Has the advantages that:
the invention discovers that the lac acid, the lac alcohol acid and the cedar acid can enhance the proliferation inhibition effect of Taxol on A2780/Taxol cells to different degrees, improve the sensitivity of the cells on Taxol and can be developed into a medicament for reversing the drug resistance of ovarian cancer to Taxol.
Drawings
FIG. 1 shows chemical structural formulas of Lacca acid, Lacca alcohol acid, cedrol and cedrol;
FIG. 2 shows the reversal of the resistance of the individual compounds to ovarian cancer cells A2780/Taxol.
Detailed Description
The following examples are given to illustrate the essence of the present invention, but not to limit the scope of the present invention.
First, experimental material
The lithospermic acid, lithospermic alcohol acid, cedaric acid and cedrol are prepared by self, the purity is more than or equal to 98%, and the structural formula is shown in figure 1. Taxol (Taxol) is purchased from Xian kang Nuo chemical Co., Ltd, and has a purity of more than or equal to 98%. Dimethyl sulfoxide (DMSO) was purchased from Sigma. Tetramethylthiazole light blue (MTT) was purchased from Biyuntian Biotech research institute.
Fetal bovine serum, DMEM medium was purchased from Gibco.
Human ovarian cancer paclitaxel-resistant cell strain A2780/Taxol was purchased from Shanghai Meixuan Biotech Co., Ltd.
Second, Experimental methods
1. Cell culture
DMEM medium containing 10% fetal calf serum at 37 deg.C and 5% CO2Culturing a paclitaxel resistant cell strain A2780/taxol of human ovarian cancer in a cell culture box, digesting, collecting, centrifuging and passaging the cells by pancreatin after the cells grow over 70-80% of the bottom of a culture bottle, and taking the cells in a logarithmic growth phase for experiment.
2. Reversal of the resistance of the Compounds to A2780/Taxol
Taking human ovarian cancer cells A2780/Taxol which grow in logarithmic phase, adjusting cell density according to 8 × 10 per hole3Inoculating each cell in a 96-well plate, adding 180 μ L of cell suspension into each well, culturing for 24h, adding lacceric acid, suberic acid or cedrol with final concentration of 10 μ M, and Taxol with different concentrations, wherein the final concentrations are 0, 1, 5, 25, 125, 250 μ g/mL respectively, and the total volume of each well is 200 μ L; the control wells were left without drug; the zero setting hole is culture solution without cells, and each group is provided with 3 multiple holes. Placing at saturated humidity, 37 deg.C and 5% CO2And (3) continuously culturing for 48h in the incubator, adding 10 mu L of MTT (5mg/mL) into each well, continuously culturing for 4h, discarding the culture supernatant, adding 150 mu L of DMSO into each well, shaking on a shaking table for 10min, measuring the OD570 value of each well, and calculating the inhibition rate of Taxol on A2780/Taxol cell proliferation, the IC50 value and the drug resistance index.
The calculation formula is as follows: cell growth inhibition (%) [1- (experimental OD value-blank OD value)/(control OD value-blank OD value) ] × 100%; calculating an IC50 value by adopting SigmaPlut 10.0 software; drug resistance reversal fold (RI) ═ cell IC50 before drug action/cell IC50 after action.
3. Statistical method
Statistical analysis is carried out by adopting SPSS17.0, the comparison between two groups adopts t test, and the difference is that P is less than 0.05, which has statistical significance.
Third, experimental results
The results are shown in Table 1 and FIG. 2, and the lac acid, lac alcohol acid and cedrol acid can enhance the proliferation inhibition effect of Taxol on A2780/Taxol cells to different degrees, improve the sensitivity of the cells on Taxol, and have no obvious effect on cedrol. The results show that the lac acid, lac alcohol acid and cypress acid can reduce the resistance of A2780/Taxol cells to Taxol.
TABLE 1 reversal of the drug resistance of the individual compounds to ovarian cancer cells A2780/Taxol
| IC50(μg/mL) | Reversal multiple of drug resistance | |
| Taxol | 31.58 | / |
| Lacca acid | 3.95 | 7.99 |
| Lacca alcohol acid | 2.77 | 11.40 |
| Cedarwood acid | 6.24 | 5.06 |
| Cedrol | 29.81 | 1.06 |
In conclusion, the lac acid, the lac alcohol acid and the cedar acid can be developed into a drug for reversing the drug resistance of ovarian cancer to the taxol.
The above-described embodiments are intended to be illustrative of the nature of the invention, but those skilled in the art will recognize that the scope of the invention is not limited to the specific embodiments.
Claims (1)
1. The application of the Lacca acid in preparing the medicine for reversing the drug resistance of ovarian cancer refers to reversing the drug resistance of the ovarian cancer to paclitaxel.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201811167944.2A CN109223746B (en) | 2018-10-08 | 2018-10-08 | Application of lithospermic acid in reversing drug resistance of ovarian cancer to paclitaxel |
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| CN201811167944.2A CN109223746B (en) | 2018-10-08 | 2018-10-08 | Application of lithospermic acid in reversing drug resistance of ovarian cancer to paclitaxel |
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| CN109223746A CN109223746A (en) | 2019-01-18 |
| CN109223746B true CN109223746B (en) | 2020-12-18 |
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| JP2007039421A (en) * | 2005-08-01 | 2007-02-15 | Ivy Cosmetics Corp | Skin care preparation for ameliorating roughened skin |
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Inventor after: Kan kinbo Inventor after: Zhang Luyan Inventor after: Li Juanjuan Inventor after: Zheng Jiarong Inventor after: Qu Weiping Inventor after: Wan Chao Inventor before: Zheng Jiarong Inventor before: Qu Weiping Inventor before: Wan Chao |
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Effective date of registration: 20201130 Address after: Room 204, unit 2, building 2, No. 529, Yangcheng Fourth Road, Yangxin County, Binzhou City, Shandong Province Applicant after: Kan kinbo Address before: 223001 room 112, Han Hou Avenue, qingJiangpu District, Huaian, Jiangsu, 112 Applicant before: HUAI'AN ANLAI BIOTECHNOLOGY Co.,Ltd. |
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