Inhibition effect of nobiletin as BH3 mimetic drug on small cell lung cancer and synergistic effect of nobiletin and histone deacetylase inhibitor

A small cell lung cancer, nobiletin technology, applied in the field of cancer research, can solve the problems of nobiletin treatment of small cell lung cancer, nobiletin and vorinostat combination treatment of small cell lung cancer and other problems

Active Publication Date: 2021-06-25
PEKING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Nobiletin has anti-tumor effect, and vorinostat has the effect of treating lung cancer. The prior art does not disclose that Nobile...

Method used

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  • Inhibition effect of nobiletin as BH3 mimetic drug on small cell lung cancer and synergistic effect of nobiletin and histone deacetylase inhibitor
  • Inhibition effect of nobiletin as BH3 mimetic drug on small cell lung cancer and synergistic effect of nobiletin and histone deacetylase inhibitor
  • Inhibition effect of nobiletin as BH3 mimetic drug on small cell lung cancer and synergistic effect of nobiletin and histone deacetylase inhibitor

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 48 potential active compounds were screened from 140,000 natural product libraries and more than 300,000 synthetic compound libraries, and then evaluated by the 5 principles of Lipinski-like drugs, and 8 potential BH3 analog compounds were obtained. Nobiletin, a compound with higher Fit value, was selected for further research, and its structural formula is

[0023]

Embodiment 2

[0025] Using surface plasmon resonance technology (SPR) to ABT263 ( figure 1 In A, the BH3 analog drug already on the market) was used as the positive control drug to discover nobietin ( figure 1 Middle B) There is dose-dependent binding to BCL-2 protein. Molecular docking results showed that nobiletin also significantly combined with other members of the BCL-2 family, BCL-XL and MCL-1.

Embodiment 3

[0026] Example 3 Comparative study of nobiletin inhibiting the survival rate of NSCLC cell A549 and SCLC cell H82

[0027] Experimental method: Collect the cultured A549 cells or NCI-H82 cells into a 15mL centrifuge tube, and centrifuge at 1000rpm for 5min. Discard the supernatant, add RPMI1640 medium to dilute the cells, adjust the cell concentration to 20000 cells / mL, and add 100 μL to each well of a 96-well culture plate. Use RPMI1640 medium to prepare different concentrations of AD23 and add to each well of the culture plate, 37 ° C, 5% CO 2 Incubate for 24h. After drug incubation, 20 μL of MTS solution was added to each well, and the incubation was continued for 3 h. The absorbance (Absorbance, O.D.) of each well was measured using a microplate reader, and the detection wavelength was 490 nm.

[0028] The administration concentrations of nobiletin (AD23) were 0 μM (con), 0.01 μM, 0.1 μM, 1 μM, 20 μM, 40 μM, 60 μM, 80 μM, 100 μM and 200 μM).

[0029] Experimental resul...

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Abstract

The invention provides application of nobiletin as a BH3 mimetic drug and/or a histone deacetylase inhibitor in preparation of drugs for treatment or adjuvant treatment of small cell lung cancer; or the nobiletin is used as a BH3 mimetic drug and/or a histone deacetylase inhibitor to prepare a product for inhibiting small cell lung cancer cell proliferation. Experimental results show that nobiletin shows a stronger inhibition effect on small cell lung cancer compared with non-small cell lung cancer. Moreover, according to the cell survival rate observed 24 hours after administration, the fixed vorinostat concentration is 1 [mu]M, AD23 can generate a high synergistic effect in a range of 0.1-100 [mu]M, and if the fixed AD23 is 3 [mu]M, the vorinostat has a high synergistic effect in a range of 1-30 [mu]M.

Description

technical field [0001] The invention relates to the field of cancer research, in particular to the inhibitory effect of nobiletin as a BH3 analog drug on small cell lung cancer and its synergistic effect with histone deacetylase inhibitors. Background technique [0002] The morbidity and mortality of lung cancer are increasing year by year worldwide, and about 85% of them are non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKI) targeting epidermal growth factor receptor (EGFR) can be effectively treated For NSCLC with EGFR mutation, three generations of TKIs have been used clinically. Small cell lung cancer (SCLC) accounts for about 15% of the total number of lung cancers. It is characterized by strong invasion, early metastasis, and poor prognosis. The first-line treatment drugs are platinum and etoposide or irinotecan. Although these two types of lung cancer are sensitive to targeted drugs and chemotherapy drugs respectively, they are prone to drug resista...

Claims

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Application Information

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IPC IPC(8): A61K31/352A61K31/16A61P35/00
CPCA61K31/352A61K31/16A61P35/00A61K2300/00
Inventor 李学军张波李玉倩孙世国陈文潘燕铁璐张岳
Owner PEKING UNIV
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