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Action mechanism and application of fangchinoline in resisting conjunctival melanoma

A technology of fangxinorine and melanoma, which is applied to the mechanism and application field of fangxinorine in anti-conjunctival melanoma, can solve the biological problems of high recurrence rate, difficult drug delivery, and no prediction or diagnosis of conjunctival melanoma. Markers etc.

Pending Publication Date: 2021-04-16
EAST CHINA UNIV OF SCI & TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Conjunctival melanoma is often treated clinically with cryotherapy, radiotherapy, and chemotherapy with mitomycin C and recombinant human interferon α-2B after local surgical treatment, but the special lesion tissue of the eye has serious drug delivery difficulties , leading to poor prognosis with drug treatment, and the 5-year recurrence rate is as high as 26%-61%
[0003] Conjunctival melanoma suffers from very few patients, its pathogenesis is extremely complex, and its incubation period is long, which makes clinical diagnosis and treatment difficult
Unfortunately, despite its similarities to cutaneous and mucosal melanomas, there are currently no biomarkers for the prediction or diagnosis of conjunctival melanoma, and there are no clinically effective agents or consensus treatment options

Method used

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  • Action mechanism and application of fangchinoline in resisting conjunctival melanoma
  • Action mechanism and application of fangchinoline in resisting conjunctival melanoma
  • Action mechanism and application of fangchinoline in resisting conjunctival melanoma

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0103] The preparation method of the probe of the present invention comprises the steps of:

[0104] (a) provide the mixed solution of fangchinoline base and iodoethyl-3-(but-3-ynyl) diaziridine in DMF;

[0105] (b) reacting the mixed solution in the step (a) for the reaction time t0 under the action of potassium carbonate to obtain the mixed product.

[0106] (c) extract and separate the mixed product in step (b) after cooling, dry, and then use column separation to obtain the probe.

[0107] In another preferred example, the mixed solution contains fangchinoline base 0.1-0.3mmol, preferably 0.2mmol;

[0108] 0.1-0.3 mmol of iodoethyl-3-(but-3-ynyl) diaziridine, preferably 0.22 mmol;

[0109] Containing DMF solution 1-3ml, preferably 2ml.

[0110]In another preferred embodiment, the reaction is carried out at 30-50°C, preferably at 25-45°C, more preferably at 40°C.

[0111] In another preferred example, t0 is 40-60 hours, preferably 45-50 hours, more preferably 48 hours. ...

Embodiment 1

[0122] Example 1: Inhibitory Effect of Fangchinoline on the Proliferation of Han Chinese Conjunctival Melanoma CM-AS16 Cells

[0123] The Han Chinese conjunctival melanoma CM-AS16 cells used in the experiment came from the Ninth People’s Hospital of Shanghai Jiaotong University, culture medium 1640H containing 10% FBS (Invitrogen, USA), 100U / mL penicillin and 100U / mL streptomycin, cultured at 37°C, containing 5%CO 2 and cultured in an incubator with saturated humidity, subcultured and digested with 0.25% trypsin, and the cells in the logarithmic growth phase were used for the CCK-8 experiment. CM-AS16 cells in 1 × 10 4 The density of cells / well was inoculated in 96-well plate, and the drug was added after the cells adhered to the wall. The final concentrations of drugs added to the 96-well plate were 100 μM, 50 μM, 25 μM, 12.5 μM, 6.25 μM, 3.12 μM, 1.56 μM, 0.78 μM and 0.39 μM, respectively. A positive control drug MEK162 group and a blank control group were set up. After ...

Embodiment 2

[0125] Example 2: Transcriptome sequencing results found that fangchinoline can regulate homologous recombination pathway

[0126] 8μM fangchinoline was co-incubated with CM-AS16 cells, and a control group without drug stimulation was set at the same time. After 24h, the old cell culture medium was removed, the cells were washed 1-2 times with 1×PBS buffer, and Trizol lysate was added (by 5×10 6 cells / ml trizol) repeatedly pipetting until fully lysed, forming a clear, transparent and non-viscous liquid, transferred to an enzyme-free centrifuge tube, stored at -80°C, and handed over to Paid Biological Company for solution identification.

[0127] The result is as figure 2 As shown, 8μM administration of fangchinoline significantly affected 9 signaling pathways (adjusted P value-5 ).

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Abstract

The invention relates to application of a compound fangchinoline with a tetrahydroisoquinoline parent nucleus in the aspect of resisting conjunctival melanoma and research on an action mechanism of the compound fangchinoline. Specifically, experiments show that fangchinoline directly targets far-end upstream binding protein 2 (FUBP2), so that gene expression of c-Myc protein is reduced, expression of key proteins RAD51 and BRCA1 of c-Myc downstream homologous recombination (HR) pathways is reduced, and the purpose of inhibiting tumor replication is achieved. The compound disclosed by the invention can be administrated together with cisplatin or olaparib to increase the anti-conjunctival melanoma drug effect and reduce the drug toxicity, so that the compound has a good clinical application prospect.

Description

technical field [0001] The invention belongs to the field of life science and medicine, and in particular relates to the action mechanism and application of fangchinoline in anti-conjunctival melanoma. Background technique [0002] Conjunctival melanoma is a rare but potentially fatal ocular tumor that seriously endangers human health, accounting for 2% of all ocular malignancies, with an annual incidence of 0.2-0.5 per million in Western countries and an incidence of Asians. 0.15 / million. Conjunctival melanoma is mostly secondary to the malignant transformation of conjunctival pigmented nevi and primary acquired melanosis of the conjunctiva. It can occur in any part of the conjunctiva of the eye, and quickly metastasize to other structures of the eye, and can also infiltrate to the ear and nose. , neck, lungs, liver, skin and even the brain. Conjunctival melanoma is often treated clinically with cryotherapy, radiotherapy, and chemotherapy with mitomycin C and recombinant ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4748A61K45/06A61P35/00C07D491/18
Inventor 李剑贾仁兵包可婷魏金莲李若曦毛斐李甬芸
Owner EAST CHINA UNIV OF SCI & TECH
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