Cancer cell‑specific anticancer effects of Coptis chinensis on gefitinib‑resistant lung cancer cells are mediated through the suppression of Mcl‑1 and Bcl‑2

Kim,Jae Hwan; Ko,Eun Sun; Kim,Dasom; Park,Seong‑Hee; Kim,Eun‑Jung; Rho,Jinkyung; Seo,Hyemin; Kim,Min Jung; Yang,Woong Mo; Ha,In Jin; Park,Myung‑Jin; Lee,Ji‑Yun

doi:10.3892/ijo.2020.5025

Cancer cell‑specific anticancer effects of Coptis chinensis on gefitinib‑resistant lung cancer cells are mediated through the suppression of Mcl‑1 and Bcl‑2

Authors:
- Jae Hwan Kim
- Eun Sun Ko
- Dasom Kim
- Seong‑Hee Park
- Eun‑Jung Kim
- Jinkyung Rho
- Hyemin Seo
- Min Jung Kim
- Woong Mo Yang
- In Jin Ha
- Myung‑Jin Park
- Ji‑Yun Lee
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Affiliations: Department of Pathology, Korea University College of Medicine, Seoul 02841, Republic of Korea, Department of Acupuncture and Moxibustion, College of Oriental Medicine, Dongguk University, Gyeongju‑si, Gyeongsangbuk‑do 38066, Republic of Korea, Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea, Department of Biological Sciences, Sookmyung Women's University, Seoul 04310, Republic of Korea, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, Korean Medicine Clinical Trial Center (K‑CTC), Kyung Hee University Korean Medicine Hospital, Seoul 02447, Republic of Korea, Division of Radiation Cancer Research, Research Center for Radio‑Senescence, Korea Institute of Radiological and Medical Sciences, Seoul 02841, Republic of Korea
Published online on: March 24, 2020 https://doi.org/10.3892/ijo.2020.5025
Pages: 1540-1550

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Abstract

The epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitor (TKI), gefitinib, is an effective therapeutic drug used in the treatment of non‑small cell lung cancers (NSCLCs) harboring EGFR mutations. However, acquired resistance significantly limits the efficacy of EGFR‑TKIs and consequently, the current chemotherapeutic strategies for NSCLCs. It is, therefore, necessary to overcome this resistance. In the present study, the anticancer potential of natural extracts of Coptis chinensis (ECC) against gefitinib‑resistant (GR) NSCLC cells were investigated in vitro and in vivo. ECC inhibited the viability, migration and invasion, and effectively induced the apoptosis of GR cells. These effects were associated with the suppression of EGFR/AKT signaling and the expression of anti‑apoptotic proteins, Mcl‑1 and Bcl‑2, which were overexpressed in GR NSCLC cells. Combination treatment with ECC and gefitinib enhanced the sensitivity of GR cells to gefitinib in vitro, but not in vivo. However, ECC increased the survival of individual zebrafish without affecting the anticancer effect to cancer cells in vivo, which indicated a specific cytotoxic effect of ECC on cancer cells, but not on normal cells; this is an important property for the development of novel anticancer drugs. On the whole, the findings of the present study indicate the potential of ECC for use in the treatment of NSCLC, particularly in combination with EGFR‑TKI therapy, in EGFR‑TKI‑resistant cancers.

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