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Archive > Volume 24 Issue 10 > 2017,24(10):1070-1075. DOI:10.3872/j.issn.1007-385X.2017.10.005 Prev Next
Basic Research
Reversal effect of extracts from stellera chamaejasme L on EGFR-TKI resistance in lung adenocarcinoma H1975 cells and its mechanism
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Abstract:
Objective: To investigate the reversal effects of the extracts from stellera chamaejasme L (SCL) on EG-FR-TKI (epidermal growth factor receptor tyrosine kinase inhibitors) resistance in lung adenocarcinoma H1975 cells, and to explore the underlying mechanism. Methods: The inhibitory effects of SCL, gefitinib, and SCL plus ge-fitinib on the proliferation of H1975 cells were evaluated by MTT assay; the effects on apoptosis of H1975 cells were determined by flow cytometry ( FACS); Wound healing assay was performed to examine cell migration; and Western blotting was conducted to detect the expression of p-EGFR and apoptosis-related protein Bcl-2. Nude mice xenograft model was constructed, and the volume of xenografts as well as the overall survival (OS) was observed after treatment with SCL plus gefitinib. Moreover, ELISA was carried out to detect the serum levels of Bcl-2 and p-EGFR. Results: IC 50 of SCL and gefitinib on H1975 cells was (21.35±2.11）mg/ml and (11.21±1.68) μmol/L, re-spectively. Compared with single treatment of SCL(5 mg/ml) or Gefitnib(1 μmol/L), combined treatment of SCL and gefitnib significantly inhibited the proliferation rate of H1975 cells ([49.78±7.09]% vs [12.88±3.64]%, [8.45±2.57]%; all P<0.01), and inhibited the migration of H1975 cells ([22.4±6.5]% vs [70.3±4.9]%, [67.1±10.5]%; all P<0.01). FACS showed that the apoptosis rate in combined treatment group was obviously higher than that in single treatment group ([51.68±6.56]% vs [9.88±2.71]%, [9.48±2.45]%; all P<0.01). Western blotting showed the protein expressions of Bcl-2 and p-EGFR in H1975 cells were remarkably decreased after the combined treatment of SCL and gefitinib (P<0.01)．In vivo xenograft experiment showed that combined treatment of SCL and gefitinib signifi-cantly inhibited progressive tumor growth and promoted the survival time compared with single treatment of SCL or gefitinib (all P<0.01). Conclusion: SCL might reverse the EGFR-TKI resistance in H1975 cells. The potential mech-anism might be related to phosphorylation of EGFR and down-regulation of Bcl-2 expression, which might provide new thoughts of treating lung adenocarcinoma.
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Project Supported:
Project supported by Medical and Health Technology Development Pro-gram of Shandong Province （No.2016WS0324)
Clc Number:
