CN115300500A - Application of psoralen in medicine for treating human skin T cell lymphoma - Google Patents
Application of psoralen in medicine for treating human skin T cell lymphoma Download PDFInfo
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- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
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- A61K36/487—Psoralea
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Abstract
The invention discloses an application of psoralen in a medicament for treating human skin T cell lymphoma; psoralen promotes apoptosis of Hut-78 by activating apoptosis signal pathway related gene expression of human skin T cell lymphoma cell strain Hut-78; psoralen promotes the expression of the mRNA of CASPASE9, can promote the expression of the mRNA of CASPASE3 and FAS/FASL, and can reduce the expression of the mRNA of BCL 2; provides a new idea for treating the T cell lymphoma of human skin.
Description
Technical Field
The invention belongs to the technical field of research and development of human skin T cell lymphoma treatment medicines, and particularly relates to application of psoralen in a human skin T cell lymphoma treatment medicine.
Background
T-cell lymphomas are a type of malignant clonal proliferative disease derived from T lymphocytes, a relatively common type of lymphoma in asian countries. NK/T cell lymphoma (Natural Killer/Tcelllymphoma) is a subtype of non-Hodgkin lymphoma, the incidence rate is the first of T cell lymphoma, and the incidence rate in China is far higher than that in Western countries. Peripheral T cell lymphomas such as extranodal nasal NK/T cell lymphomas and cutaneous T cell lymphomas have the characteristics of high invasiveness, rapid disease progression, short life cycle, poor prognosis and the like, and pose a serious threat to the life health of people in China.
Coumarin, flavonoid, monoterpene phenol, stigmasterol, sitosterol glucoside, raffinose, etc. are separated from fructus Psoraleae, wherein the coumarin, flavonoid and monoterpene phenol compounds are main active ingredients. Psoralens and isopsoralens belong to the coumarin class of compounds. Psoralen (Psoralen) has the chemical formula: c 11 H 6 O 3 Colorless needle-shaped crystal with volatility, and is dissolved in methanol, ethanol, benzene, chloroform and acetone; slightly soluble in water, diethyl ether and petroleum ether. The inhibitory effect of Psoralen (Psoralen) on T cell lymphoma cell lines and its mechanism are not clear at present.
Disclosure of Invention
The invention obtains that the psoralen has the effect of promoting apoptosis on the T cell lymphoma cells of human skin by researching the action mechanism of the psoralen on the T cell lymphoma cell strains of the human skin;
the application of psoralen in the medicine for treating human skin T cell lymphoma;
preferably, the psoralen promotes the apoptosis of Hut-78 by activating the expression of genes related to the apoptosis signal pathway of the human skin T cell lymphoma cell strain Hut-78;
preferably, the psoralen promotes the expression of cellular CASPASE9 mRNA, and can promote the expression of CASPASE3, FAS/FASLmRNA and down-regulate the expression of BCL2 mRNA.
The invention has the beneficial effects that:
the psoralen promotes apoptosis of human skin T cell lymphoma cell strain Hut-78, can be used for a human skin T cell lymphoma treatment drug, and provides a new idea for human skin T cell lymphoma treatment.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a graph of the inhibitory effect of Psoralen (Psoralen) on Hut-78 cell proliferation; wherein A: no administration of the blank group; b: the 50 mu M, 100 mu M, 200 mu M and 400 mu M osteopontin can obviously inhibit the growth of Hut-78 cells;
FIG. 2 is a graph of the effect of different concentrations of Psoralen (Psoralen) on Hut-78 cell proliferation and apoptosis (n = 8); wherein A: the effect of different concentrations of Psoralen (Psoralen) on Hut-78 cell proliferation and apoptosis; b: IC50 value profile for Psoralen (Psoralen) inhibition of Hut-78 cell proliferation;
FIG. 3 is the effect of Psoralen (400 μ M) on apoptosis signaling pathway gene expression in Hut-78 cells (n = 3); a: effect of Psoralen on Bcl2 gene expression, B: impact of Psoralen on Bax gene expression, C: effect of Psoralen on FAS gene expression, D: (ii) the effect of Psoralen on FASL gene expression; the influence of Psoralen on the expression of Caspase3 gene; f: (ii) Psoralen effect on Caspase8 gene expression; g: psoralen effects on Caspase9 gene expression.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
The application of psoralen in the medicine for treating human skin T cell lymphoma;
preferably, the psoralen promotes the apoptosis of Hut-78 by activating the expression of genes related to the apoptosis signal pathway of the human skin T cell lymphoma cell strain Hut-78;
preferably, the psoralen promotes the expression of cellular CASPASE9 mRNA, and can promote the expression of CASPASE3, FAS/FASLmRNA and down-regulate the expression of BCL2 mRNA.
Example 2
Verifying psoralen to Hut-78 cell apoptosis and apoptosis related gene expression experiment;
1. materials: the human skin T cell lymphoma cell strain Hut-78 is purchased from the prominent innovation center of molecular cell science of Chinese academy of sciences. Psoralen (purity > 98%) was purchased from the chinese food and drug administration research institute. RPMI-1640 medium (Ginco) was purchased from Life technology, inc.; fetal bovine serum (Gibco) was purchased from Life technology, inc. CCK-8 reagent, RNA extraction kit and reverse transcription reagent were purchased from TransGenBiotech, inc., beijing, all-purpose gold Biotech. RNA amplification primers were ordered from Biotechnology engineering (Shanghai) GmbH.
2. Method of producing a composite material
1) Hut-78 cell culture
Hut-78 cells were cultured in RPMI-1640 medium (100U. Ml) containing 20% fetal bovine serum -1 Penicillin and 100. Mu.g/ml -1 Streptomycin double antibody), 37 ℃ and 5% CO 2 Culturing and subculturing in an incubator;
2) Determination of cell proliferation and apoptosis
Taking Hut-78 cells in logarithmic growth phase according to the ratio of 1.0 multiplied by 10 4 The concentration of each well was seeded overnight in 96 well cell culture plates. The experimental groups were as follows: blank group (no drug treatment), drug treated group (after pretreatment with 25, 50, 100, 200, 400 μ M psoralen for 24h, respectively). After the treatment, 10. Mu.l of CCK-8 detection reagent is added into each well of a 96-well cell culture plate, and the proliferation and apoptosis conditions of the Hut-78 cells in each drug treatment group are respectively measured.
3) Determination of psoralen IC50
Taking Hut-78 cells in logarithmic growth phase according to the ratio of 1.0 multiplied by 10 4 The concentration of each well was seeded overnight in 96 well cell culture plates. The experimental groups were as follows: blank (no drug treatment), drug treated (after pretreatment with 25, 50, 100, 200, 400 μ M Psoralen (Psoralen) for 24h, respectively). After the treatment was completed, 10. Mu.l of CCK-8 detection reagent was added to each well of the 96-well cell culture plate. IC50 values for psoralens to inhibit proliferation and apoptosis of Hut-78 cells were determined.
4) Apoptosis-related gene expression analysis
After the cells are treated according to the grouping and drug treatment method, RNA is extracted by a Trizol method, and the concentration of the RNA is measured by a Nanodrop protein nucleic acid analyzer. Mu.g of total RNA was taken and converted into cDNA using reverse transcription kit (Thermo). The above transcription product cDNA was treated with ddH 2 O is diluted according to the proportion of 1:5 and then used as a template, the gene expression of BCL2, BAX, CASPAS3, CASPASE9 and FAS/FASL in cells is quantified according to the operation instruction of the full-scale gold SYBRGreen fluorescent quantitative kit, and the internal reference gene is GAPDH. The PCR reaction conditions were as follows: the amplification reaction was carried out for 40 cycles of pre-denaturation at 95 ℃ for 30sec, and amplification at 95 ℃ for 5sec and 60 ℃ for 34 sec.
3. Results
1) Inhibition of Hut-78 cell proliferation by Psoralen (Psoralen)
As shown in fig. 1, 25 μ M osteopontin did not significantly inhibit Hut-78 cell growth after 24h of psoralen pretreatment compared to the blank group, whereas 50 μ M, 100 μ M, 200 μ M, 400 μ M osteopontin all significantly inhibited Hut-78 cell growth (P <0.001, P <0.01, P < 0.05).
2) Cell viability (CCK-8) experiment of psoralen drug on human lymphoma cell line HUT-78 cells at cell level
The experimental results show that: psoralen can promote apoptosis of human T lymphoma cell line Hut-78 cells at a cellular level, can obviously inhibit cell viability of the T lymphoma cell line HUT-78 cells at a drug concentration of 50 mu M, and has statistical significance (p < 0.05) and an IC50 value of about 220.8 mu M, and related results are shown in figure 2.
3) Effect of Psoralen (Psoralen) on expression of genes associated with apoptosis of Hut-78 cells
Studies show that the apoptosis response of cells can be additionally induced through BCL2// BAX/Fas/FasL and Caspase3/Caspase8/Caspase9 signal channels. Consistent with literature reports, our results show (FIG. 2) that Psoralen administration significantly increases the mRNA expression of BCL2// BAX/Fas/FasL, caspase3/Caspase8/Caspase9 in Hut-78 cells. Therefore, psoralen can inhibit the activation of Hut-78 cells by regulating the expression of BCL2// BAX/Fas/FasL and Caspase3/Caspase8/Caspase9 genes, thereby promoting the apoptosis of Hut-78.
The primer sequences are shown in Table 1. As shown in figure 2, 50 μ M Psoralen (Psoralen) was able to significantly promote mRNA expression of cellular CASPASE9 (P < 0.05) and showed a trend towards promoting CASPASE3, FAS/faslmn expression, a trend towards downregulating BCL2mRNA expression, but had no significant effect on the mRNA levels of Hut-78 cellular BAX, compared to the blank group.
TABLE 1 apoptosis-related Gene primer names and sequences
Claims (3)
1. Application of psoralen in a medicament for treating human skin T cell lymphoma.
2. The application of psoralen in a human skin T-cell lymphoma therapeutic drug according to claim 1, wherein the psoralen promotes the apoptosis of Hut-78 by activating the expression of genes related to the apoptosis signal pathway of a human skin T-cell lymphoma cell strain Hut-78.
3. The use of psoralen in a medicament for the treatment of human skin T-cell lymphoma according to claim 1, wherein psoralen promotes the expression of cellular CASPASE9 mRNA, and promotes the expression of CASPASE3, FAS/FASL mRNA, down-regulating BCL2 mRNA.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211137135.3A CN115300500A (en) | 2022-09-19 | 2022-09-19 | Application of psoralen in medicine for treating human skin T cell lymphoma |
| LU503942A LU503942B1 (en) | 2022-09-19 | 2023-04-14 | Use of psoralen in therapeutic agents for human cutaneous T-cell lymphoma |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4999375A (en) * | 1989-04-11 | 1991-03-12 | Hoffmann-La Roche Inc. | Psoralen reagent compositions for extracorporeal treatment of blood |
| US7282343B1 (en) * | 2000-10-24 | 2007-10-16 | Intracell, Llc | Compositions, methods and kits for diagnosis and treatment of Chlamydia pneumoniae infections of the skin and those associated with cutaneous T-cell lymphoma |
| CN101287493A (en) * | 2005-08-18 | 2008-10-15 | 根马布股份公司 | Therapy with cd4 binding peptides and radiation |
-
2022
- 2022-09-19 CN CN202211137135.3A patent/CN115300500A/en active Pending
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- 2023-04-14 LU LU503942A patent/LU503942B1/en active IP Right Grant
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4999375A (en) * | 1989-04-11 | 1991-03-12 | Hoffmann-La Roche Inc. | Psoralen reagent compositions for extracorporeal treatment of blood |
| US5036102A (en) * | 1989-04-11 | 1991-07-30 | Hoffmann-La Roche Inc. | Method of treating autoimmune diseases comprising administration of psoralen dosage forms |
| US7282343B1 (en) * | 2000-10-24 | 2007-10-16 | Intracell, Llc | Compositions, methods and kits for diagnosis and treatment of Chlamydia pneumoniae infections of the skin and those associated with cutaneous T-cell lymphoma |
| CN101287493A (en) * | 2005-08-18 | 2008-10-15 | 根马布股份公司 | Therapy with cd4 binding peptides and radiation |
Non-Patent Citations (3)
| Title |
|---|
| WALTER LISZEWSKI等: "Psoralen with ultraviolet A-induced apoptosis of cutaneous lymphoma cell lines is augmented by type I interferons via the JAK1–STAT1 pathway", PHOTODERMATOL PHOTOIMMUNOL PHOTOMED, vol. 33, pages 164 - 171 * |
| 崔小庆，沈素芸，杨易灿: "补骨脂素加长波紫外线对白血病细胞杀伤作用的实验研究", 临床血液学杂志, no. 04, pages 166 - 167 * |
| 邹丹丹;粟丽雷;邹旭辉;王梦婷;邹勇莉;: "原发性皮肤淋巴瘤研究进展", 皮肤病与性病, no. 01, pages 24 - 27 * |
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| LU503942B1 (en) | 2023-10-16 |
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