Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Root Extract of Scutellaria Baicalensis Increases Gefitinib Sensitivity in H1975 Human Non-small Cell Lung Cancer Cells

H1975 세포에서 황금추출물에 의한 gefitinib 저항성 억제 효과

  • Park, Shin-Hyung (Department of Pathology, College of Korean Medicine, Dong-eui University) ;
  • Park, Hyun-Ji (Department of Pathology, College of Korean Medicine, Dong-eui University)
  • 박신형 (동의대학교 한의과대학 병리학교실) ;
  • 박현지 (동의대학교 한의과대학 병리학교실)
  • Received : 2021.07.06
  • Accepted : 2021.08.20
  • Published : 2021.08.25
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Abstract

Gefitinib, a first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), provides obvious clinical benefit in patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, patients ultimately develop gefitinib resistance which mainly caused by EGFR T790M secondary mutation. In the current study, we investigated whether the root extract of Scutellaria baicalensis (SB) overcomes gefitinib resistance. Gefitinib-resistant H1975 human NSCLC cells (EGFR L858R/T790M double mutant) were treated with gefitinib and/or ethanol extract of SB (ESB) to evaluate the effect of ESB on the gefitinib sensitivity. The cell viability was measured by MTT assay and trypan blue exclusion assay. The colony-forming ability was evaluated by anchorage-dependent colony formation assay. Combined treatment with gefitinib and ESB markedly decreased the cell viability and colony formation than single treatment with gefitinib or ESB in H1975 cells. In addition, cells treated with both gefitinib and ESB exhibited a significant increase of sub-G1 DNA content which indicates apoptotic cells compared with those treated with gefitinib or ESB alone. As a molecular mechanism, combined treatment with gefitinib and ESB strongly downregulated the phosphorylation of ERK and JNK than single treatment with gefitinib or ESB. Taken together, our results demonstrate that ESB sensitizes H1975 cells to gefitinib treatment. We cautiously propose that ESB can be used in combination with gefitinib for the advanced NSCLC patients with acquired resistance to EGFR TKIs.

Keywords

Acknowledgement

본 연구는 한국연구재단의 기본연구(No. NRF-2019R1F1A1059588) 및 우수신진연구(No. NRF-2021R1C1C100506211)의 사업비로 수행되었음.

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