4.6 Article

The Effects of Artesunate on the Expression of EGFR and ABCG2 in A549 Human Lung Cancer Cells and a Xenograft Model

Journal

MOLECULES
Volume 16, Issue 12, Pages 10556-10569

Publisher

MDPI
DOI: 10.3390/molecules161210556

Keywords

EGFR; ABCG2; Akt; artesunate; NSCLC; multi-drug resistance

Funding

  1. National Natural Science Foundation of China [81071786, 81172070]
  2. CSTC [2011AB5032]
  3. Military Clinical high-tech [2010gxjs070]
  4. National High Technology Research and Development Program of China [2008AA02Z104]

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Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Clinical and laboratory studies have suggested that multi-targeting approaches against neoplastic cells could help to increase patient survival and might reduce the emergence of cells that are resistant to single-target inhibitors. Artesunate (ART) is one of the most potent and rapidly acting antimalarial agents known, and it also exerts a profound cytotoxic activity toward cancer cells and reverses multi-drug resistance. In the present study, we found that artesunate inhibited NSCLC A549 cell growth and proliferation, induced apoptosis and suppressed tumor growth in a dose-dependent manner in A549 cells and a mouse xenograft model. Furthermore, artesunate down-regulated the expression of epidermal growth factor receptor (EGFR), Akt and ATP-binding cassette subfamily G member 2 (ABCG2) at the mRNA and protein levels in vitro and in vivo. In conclusion, artesunate is an effective anti-cancer drug that may enhance the effectiveness of other anticancer drugs and may reverse multi-drug resistance by suppressing the transcription of ABCG2, which inhibits drug efflux.

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