Tanshinone IIA inhibits cell proliferation and tumor growth by downregulating STAT3 in human gastric cancer

Zhang,Yongjun; Guo,Shuguang; Fang,Jian; Peng,Bojian; Zhang,Yuan; Cao,Tiansheng

doi:10.3892/etm.2018.6562

Tanshinone IIA inhibits cell proliferation and tumor growth by downregulating STAT3 in human gastric cancer

Authors:
- Yongjun Zhang
- Shuguang Guo
- Jian Fang
- Bojian Peng
- Yuan Zhang
- Tiansheng Cao
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Affiliations: Department of Gastroenterology, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong 510800, P.R. China, Physical Examination Center, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510006, P.R. China, Department of Pharmacology, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong 510800, P.R. China, Department of General Surgery, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong 510800, P.R. China
Published online on: August 2, 2018 https://doi.org/10.3892/etm.2018.6562
Pages: 2931-2937
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer is the third leading cause of cancer‑associated deaths worldwide. Research into the underlying mechanisms of gastric cancer is essential for the development of novel therapeutic agents to improve the prognoses of patients with gastric cancer. Tanshinone IIA (Tan IIA) is the pure extract of Danshen root (Salvia miltiorrhiza) and has been report to inhibit the proliferation of gastric cancer cells; however, the intrinsic underlying mechanisms remain unclear. The aim of the present study was to investigate whether Tan IIA has a direct anti‑cancer effect in gastric cancer cells and determine the underlying mechanisms responsible. The results revealed that Tan IIA effectively inhibits proliferation in three human gastric cancer cell lines (SNU‑638, MKN1 and AGS) in a time‑ and dose‑dependent manner. Furthermore, Tan IIA treatment induced an increase in apoptosis, B‑cell lymphoma (Bcl‑2)‑associated protein X expression and cleaved caspase‑3 levels, as well as a decrease in Bcl‑2 expression. Treatment with Tan IIA inhibited Furthermore, treatment with Tan IIA significantly inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which may be responsible for the changes in apoptosis gene expression. However, overexpression of STAT3 significantly ameliorated the Tan IIA‑induced suppression of cell growth and apoptosis. A nude mouse xenograft model was constructed and the results revealed that intraperitoneal Tan IIA treatment for 28 days significantly inhibited tumor growth and STAT3 activation. The results of the present study suggest that Tan IIA exerts potent anti‑cancer activity in gastric cancer cells and this effect is mediated by the downregulation of STAT3 activation.

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