High-flux anti-tumor drug screening cell model based on STAT3 and NF-kB two-signal channel serving as target, as well as building and application of high-flux anti-tumor drug screening cell model

Abstract

The invention provides a high-flux anti-tumor drug screening cell model based on an STAT3 and NF-kB two-signal channel serving as a target. In the cell model, the specific binding sequence of STAT3 and that of NF-kB are bound to build a reporting system carrier; and the cell model is built by binding competent cells comprising both constitutive STAT3 and constitutive NF-kB. The cell model is used for screening and treating cell cancerization caused by continuous activization of STAT3 and / or NF-kB, and medicines generated by the combination and the mutual promotion of STAT3 and NF-kB, and has a higher efficiency than a single-signal medicine screening system. As the competent cells comprising both constitutive STAT3 and constitutive NF-kB are adopted, the reporting gene in the cell model is in a highly active state, no stimulus is required to be added additionally, the screening process is simplified, the screening cost is reduced, the stability, the high efficiency and the easiness in the use of a system are improved, and the cell model is more suitable for high-flux medicine screening.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a cell model for screening anti-tumor drugs, in particular to a high-throughput cell model for screening anti-tumor drugs based on dual signaling pathways of STAT3 and NF-κB; Construction method and application of cell model for anti-tumor drug screening. Background technique [0002] In many tumor cells, especially in colon cancer, breast cancer, glioma cells, lung cancer and other cells, there are continuously activated STAT3 (signal transducer and activator of transcription 3) and NF-kB (nuclear factor-κB )active. The NF-κB family mainly includes the following members, specifically RelA (p65), RelB, c-Rel, p50, and p52. Usually, NF-κB exists in the form of homologous or heterodimer, among which p65 / p50 dimer Is the most common form of NF-κB in mammals. Under normal circumstances, NF-κB dimer is mainly retained in the cytoplasm due to the combination of its inhibitory protein IκB (I...

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Problems solved by technology

[0003] At present, more and more researchers have realized the feasibility of using STAT3 and NF-kB as signaling pathways for anti-tumor drug screening, and have begun to try related methods, but The drug screening system based on STAT3 and NF-kB signaling pathway as the target, because the STAT3 or NF-kB activity of the selected cell line itself is relatively low, when screening specific inhibitors, it is often necessary to stimulate the cells with cytokines in advance, and then proceed For compound screening, the use of cytokines not only greatly increases the cost, but also increases the instability of the system with each additional step of the drug screening system; at the same time, the external stimulation cannot completely simulate the fact that tumor cells actually have higher STAT3 or NF-kB activity. state

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