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Anti-cancer activity of DHA on gastric cancer—an in vitro and in vivo study

  • Research Article
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Tumor Biology

Abstract

Treatment of gastric cancer remains a major challenge, and new anticancer drugs are urgently required. This study investigated whether dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, could inhibit the growth of gastric cancer both in vitro and in vivo. A series of in vitro experiments including MTT, colony-forming, wound healing, invasion, cell cycle, cellular senescence, and apoptosis assays were performed to examine the antiproliferative and antimetastatic effects of DHA on three gastric cancer cell lines, SGC-7901, BGC823, and MGC803. The result showed that the proliferation rate and colony-forming abilities of gastric cancer cells were significantly suppressed by DHA together with significant suppression of the expressions of proliferation markers (PCNA, cyclin E, and cyclin D1), and upregulation of p21 and p27. Moreover, DHA induced cellular senescence, G1 phase cell cycle arrest and hindered the migration and invasion of gastric cancer cells corresponding with downregulation of MMP-9 and MMP-2. Furthermore, DHA significantly induced apoptosis through suppressing Bcl-2 as well as activating caspase-9 and PARP. Treatment of gastric cancer cells with DHA increased miR-15b and miR-16 expression, caused a downregulation of Bcl-2, resulting in apoptosis of gastric cancer cells. In vivo, our data showed that DHA significantly inhibited the growth of SGC7901 cell-transplanted tumors. In summary, we have shown that DHA is able to inhibit the growth and metastasis of human gastric cancer. The modulation of miR-15b and miR-16 mediated the apoptosis effects of DHA in gastric cancer cells. Our work suggested that DHA has significant anticancer effects against gastric cancer both in vivo and in vitro, indicating that it is a promising therapy for human gastric cancer.

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Abbreviations

DHA:

Dihydroartemisinin

miRNA:

MicroRNA

3′UTR:

3′ untranslated region

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

MMP-2:

Matrix metalloproteinase 2

MMP-9:

Matrix metalloproteinase 9

ELISA:

Enzyme-linked immunosorbent assay

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Conflict of interests

None.

Financial support

This study was supported by the National Natural Science Foundation of China for the youth (grant no. 81001081), the Foundation of the First Affiliated Hospital of Harbin Medical University (grant no. 2011BS018), the Foundation of Harbin Science and Technology bureau for creative young talents (grant no. 2010RFQXS069), The Foundation of Health Department of Heilongjiang Province (grant no. 2009-043). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, China

    Haijun Sun, Xianzhi Meng, Jihua Han, Bing Wang, Xuedong Bai & Xin Zhang

  2. Teaching Affairs Section, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China

    Zhe Zhang

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  1. Haijun Sun
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  2. Xianzhi Meng
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  3. Jihua Han
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  4. Zhe Zhang
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  5. Bing Wang
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  7. Xin Zhang
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Correspondence to Xianzhi Meng.

Additional information

Haijun Sun and Xianzhi Meng contributed equally to this work.

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Sun, H., Meng, X., Han, J. et al. Anti-cancer activity of DHA on gastric cancer—an in vitro and in vivo study. Tumor Biol. 34, 3791–3800 (2013). https://doi.org/10.1007/s13277-013-0963-0

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  • DOI: https://doi.org/10.1007/s13277-013-0963-0

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