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

Tumour Biol. 2013 Dec;34(6):3791-800. doi: 10.1007/s13277-013-0963-0. Epub 2013 Aug 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Artemisinins / pharmacology*
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach / drug effects*
  • Stomach / pathology
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Xenograft Model Antitumor Assays*

Substances

  • Antineoplastic Agents
  • Artemisinins
  • Cell Cycle Proteins
  • MIRN15 microRNA, human
  • MIRN16 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • dihydroartemisinin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9