Dihydroartemisinin sensitizes Lewis lung carcinoma cells to carboplatin therapy via p38 mitogen-activated protein kinase activation

Zhang,Bicheng; Zhang,Zhimin; Wang,Jun; Yang,Bo; Zhao,Yong; Rao,Zhiguo; Gao,Jianfei

doi:10.3892/ol.2018.8276

Dihydroartemisinin sensitizes Lewis lung carcinoma cells to carboplatin therapy via p38 mitogen-activated protein kinase activation

Authors:
- Bicheng Zhang
- Zhimin Zhang
- Jun Wang
- Bo Yang
- Yong Zhao
- Zhiguo Rao
- Jianfei Gao
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Affiliations: Department of Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China, Department of Oncology, General Hospital of Jinan Command, People's Liberation Army, Jinan, Shandong 250031, P.R. China
Published online on: March 15, 2018 https://doi.org/10.3892/ol.2018.8276
Pages: 7531-7536
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, is an effective novel antimalarial agent. Studies have suggested that it also exhibits anticancer effects when administered alone or in combination with conventional chemotherapeutic agents. The present study investigated the therapeutic effect of DHA combined with carboplatin (CBP) on Lewis lung carcinoma (LLC) cells and the possible underlying molecular mechanisms. MTT and clonogenic assays demonstrated that the proliferation activity of LLC cells was inhibited in a dose‑dependent manner by DHA combined with CBP. In addition, flow cytometry analysis revealed that cell cycle arrest was induced at the G0/G1 phase and apoptosis was induced following treatment with the combination. When administered in combination with CBP, DHA exhibited more effective anticancer activity compared with DHA or CBP used alone, via increased apoptosis. Following treatment with DHA with or without CBP, the expression of phosphorylated‑p38 mitogen‑activated protein kinase (MAPK), which can be inhibited with the selective inhibitor SB202190, was detected by western blotting. To summarize, the results of the present study indicated that DHA may sensitize LLC cells to CBP therapy via the activation of p38MAPK, which suggests that a combined treatment of DHA and CBP may be a potential novel therapeutic schedule for lung adenocarcinoma.

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