Triple domain protein 33 overcomes acquired resistance toosimertinib in non-small cell lung cancer through the TGF-β1 signaling pathway
YANG Yijing
XU Lu
Abstract：Objective To investigate the role of tripartietemotif-containing 33(TRIM33)in the acquired resistance to osimertinib in non-small cell lung cancer(NSCLC),and to explore its potential mechanism.Methods Using the concen-tration increasing method to construct H1975OR and HCC827OR NSCLC cells resistant to the third-generation targeted drug Osimertinib.CCK-8 assay was used to detect IC50 of the resistant cells.Western blotting was used to detect changes in TRIM33 expression levels between parental cells and drug-resistant cells.Knocking down TRIM33 by siRNA in parental cells and CCK-8 assay to investigate the effect of TRIM33 expression level on drug sensitivity.ELISA assay was used to ex-plore the relationship between TRIM33 and the secretion of transforming growth factor-β1(TGF-β1).Results After NSCLC cells acquired resistance to Osimertinib,the expression of TRIM33 in resistant cells significantly decreased.Knock-down of TRIM33 in sensitive cells decreased the sensitivity of cells to Osimertinib.ELISA assay revealed an increase in TGF-β1 secretion in drug-resistant cells,and knockdown of TRIM33 also increased the secretion of TGF-β1 in parental cells.Western blot showed that the Smad signaling pathway downstream of TGF-β1 was activated in drug-resistant cells.Conclu-sion This study found that TRIM33 plays an important role in overcoming acquired resistance in NSCLC by inhibiting TGF-β1 and its downstream signaling pathways.TRIM33 is expected to become a potential anti-drug-resistance target and prog-nostic marker in NSCLC.
Keywords：Tripartietemotif-containing 33(TRIM33)Non-small cell lung cancerAcquired resistanceTransforming growth factor-β1
Publication Date：2025-10-30
Online Publishing Date：2025-11-26(First online date of this platform, not the publication date of the document)
Pages：7( 937-942,954 )