Triptolide exerts pro-apoptotic and cell cycle arrest activity on drug-resistant human lung cancer A549/Taxol cells via modulation of MAPK and PI3K/Akt signaling pathways

Xie,Chen  Qiong; Zhou,Ping; Zuo,Jian; Li,Xiang; Chen,Yong; Chen,Jian  Wei

doi:10.3892/ol.2016.5099

Triptolide exerts pro-apoptotic and cell cycle arrest activity on drug-resistant human lung cancer A549/Taxol cells via modulation of MAPK and PI3K/Akt signaling pathways

Authors:
- Chen Qiong Xie
- Ping Zhou
- Jian Zuo
- Xiang Li
- Yong Chen
- Jian Wei Chen
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Affiliations: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China
Published online on: September 7, 2016 https://doi.org/10.3892/ol.2016.5099
Pages: 3586-3590

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Abstract

Multidrug resistance (MDR) is a major obstacle in the effective chemotherapeutic treatment of cancers. Triptolide (TPL) is a diterpenoid isolated from Tripterygium wilfordii Hook. f., a traditional Chinese medicine. It was demonstrated in our previous study that TPL exerts anti‑MDR cancers on various MDR cell lines (including A549/Taxol, MCF‑7/ADR and Bel7402/5‑Fu). The present study was designed to investigate its anti‑proliferative activity on A549/Taxol cells, and explore the underlying mechanism of action. The anti‑proliferative activity of TPL on A549/Taxol cells was assessed by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Its pro‑apoptosis and cell cycle arrest activities were analyzed by flow cytometry. Western blot assay was employed to investigate the levels of mitogen-activated protein kinases (MAPKs) and apoptosis‑related proteins in cells. TPL efficiently suppressed the proliferation of A549/Taxol cells. Co‑treatment with MAPK inhibitors in the MTT assay indicated that the extracellular signal‑regulated kinase (ERK) and c‑Jun N‑terminal kinase (JNK) pathways were involved in the process. Upregulation of p‑p38, p‑ERK, p‑GSK‑3β, Bax and cleaved caspases‑3 and ‑9, and downregulation of p‑JNK, p‑Akt and Bcl‑2 were observed upon treatment with TPL in the A549/Taxol cells. The results from flow cytometry assay revealed that TPL induced apoptosis and S‑phase arrest in A549/Taxol cells. This occurred as a result of the upregulation of p‑ERK and p‑GSK‑3β, and the downregulation of p‑JNK and p‑Akt, and was responsible for the subsequent anti-proliferative activity.

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