Application of composition to preparation of medicine for inhibiting gastric cancer cell proliferation based on regulation and control of CDKs and SMAD6 genes

A technology for gene suppression and gastric cancer cells, applied in drug combinations, active ingredients of heterocyclic compounds, medical preparations containing active ingredients, etc., can solve problems such as poor prognosis

Inactive Publication Date: 2021-05-28
HANDAN PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Studies have shown that CDK1 (cyclin-dependent kinase 1) is an important regulator of G2-M phase transition. It has been reported that CDK1 can cooperate with cyclin B to promote cells to enter meiosis. CDK1 plays an important role in CRC circulating tumor cells. CDK1 plays a key role in promoting the G2-M transition, regulating the G1 process, and the transition from G1 to S phase. Studies have shown that the increase in the expression level of CDK1 is closely related to the proliferation of cancer cells or the poor prognosis of cancer, and the high level of CDK1 Expression rate predicts poor prognosis in CRC patients

Method used

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  • Application of composition to preparation of medicine for inhibiting gastric cancer cell proliferation based on regulation and control of CDKs and SMAD6 genes
  • Application of composition to preparation of medicine for inhibiting gastric cancer cell proliferation based on regulation and control of CDKs and SMAD6 genes
  • Application of composition to preparation of medicine for inhibiting gastric cancer cell proliferation based on regulation and control of CDKs and SMAD6 genes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Moluotan is composed of lily, Poria cocos, scrophulariaceae, black medicine, Alisma, Radix Ophiopogon, Angelica, Atractylodes macrocephala, capillary, white peony root, dendrobium, calamus chinensis, Chuanxiong, notoginseng, Burnet, Corydalis, Puhuang, chicken The pure Chinese medicine preparation composed of 18 medicinal materials such as Neijin has the functions of harmonizing the stomach and invigorating the spleen, dredging collaterals, relieving pain, invigorating the spleen and reducing swelling, and can significantly reduce the expression of EGF and EGFR in patients with CAG, and the actual clinical application effect is quite good. Moluodan was selected as the treatment for chronic gastritis and chronic atrophy by the "Chinese Chronic Gastritis Consensus Opinion" (2017) formulated by the Digestive Disease Branch of the Chinese Medical Association, and the "Consensus Opinion on the Diagnosis and Treatment of Chronic Gastritis Experts in Chronic Gastritis" (2017) is...

Embodiment 2

[0057] Example 2 Material Identification of Molodan Tumor Suppressor Function

[0058] In this example, among the genes with significantly changed expression levels in the transcriptome analysis data, the changes in gene transcripts such as CDK1, CDK6, and SMAD6 were used as marker genes regulating tumor suppression from the aspect of inhibiting cell proliferation.

[0059] The SGC-7901 cell line (preserved by our laboratory and purchased from the ATCC cell bank) is used as the object of drug treatment. The cells have the characteristics of rapid reproduction and easy culture. The cultured SGC-7901 cells were seeded on a 6-well plate (50w cells were cultured in each well), and cultured in DMEM (10% FBS) medium until all adhered. The molodan candidate active components screened above were dissolved in DMSO, and applied to the SGC-7901 cell culture medium respectively, and the treated cells were collected after incubation for 24 hours. RNA was extracted according to the process...

Embodiment 3

[0063] In this example, different effective substances were selected and combined according to different molar ratios to verify the advantages of different combinations in inhibiting the proliferation of gastric cancer cells.

[0064] CCK-8 assay was used to detect cell proliferation, and SGC-7901 cells were treated with 1×10 4 The density per hole was inoculated on a 96-well plate, and the dosing treatment was carried out according to the following combination methods. The specific dosage is shown in Table 4 below:

[0065] Group 1: Limonin: Typhanoside: Rutin: Berberine: Ginsenoside F2=40:1:160:25:100;

[0066] The second group: acetine chloride: naringenin: calloic acid: corosolic acid: bougainvillea alcohol = 1:250:5:5:5;

[0067] The third group: kaempferol-3-o-rutinoside: isoquercitrin: paeonifloride glycoside: palmatine: astragalin = 75:8:10:20:100;

[0068] The fourth group: Apigenin: Atractylodes lactone III: Chrysophanol: Ellagic acid: Quercetin = 4:10:1:3:8;

[0...

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Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to application of a composition to preparation of drugs for inhibiting gastric cancer cell proliferation based on regulation and control of CDK1, CDK6 and SMAD6 genes. On the basis of fingerprint spectrum analysis of a Chinese patent medicine Morhodamine, CDK1, CDK6, SMAD6 and other cell proliferation and cancer inhibition related genes are selected as Morhodamine direct or indirect regulation target genes; therefore, active components, such as apigenin, atractylenolide III, chrysophanol, rutin, ellagic acid, quercetin, limonin, typhaneoside, berberine, ginsenoside F2, kaempferol-3-o-rutinoside, isoquercitrin, albiflorin, palmatine, astragalin, hydrogenated pinicolic acid, cinnamic acid, oleanolic acid, gamma-terpinene, notoginsenoside Fe, nitidine chloride, naringenin, traumatic acid, corosolic acid or decursinol, can be screened out. The medicine provides theoretical support for developing novel medicines for treating gastric cancer.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to the use of a composition for preparing a drug for inhibiting proliferation of gastric cancer cells based on regulating CDK1, CDK6 and SMAD6 genes. Background technique [0002] According to reports, the annual incidence of gastric cancer (GC) ranks 4th and 5th in the world, and the annual mortality rate ranks 2nd among all tumors. Although the diagnosis and treatment of gastric cancer have made great progress in recent years, its 5-year survival rate is still very low. As a highly malignant tumor, GC has the characteristics of unlimited cell proliferation, invasion, and metastasis, and it is a tumor with poor prognosis. It is of great significance to pay attention to and pay attention to the treatment and research of gastric cancer. At present, the drug treatment of tumors such as gastric cancer is facing two major problems, namely, non-specific t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/366A61K31/7048A61K31/4375A61K31/704A61K31/4741A61K31/352A61K31/201A61K31/56A61K31/37A61K31/4745A61K31/365A61K31/122A61P35/00
CPCA61K31/366A61K31/7048A61K31/4375A61K31/704A61K31/4741A61K31/352A61K31/201A61K31/56A61K31/37A61K31/4745A61K31/365A61K31/122A61P35/00A61K2300/00A61K31/575A61K31/192A61K31/015
Inventor 陈致慜殷苗苗王珍刘会云王梦蕾
Owner HANDAN PHARMA
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