Involvement of CD147 in regulation of multidrug resistance to P-gp substrate drugs and in vitro invasion in breast cancer cells

Cancer Sci. 2007 Jul;98(7):1064-9. doi: 10.1111/j.1349-7006.2007.00487.x. Epub 2007 Apr 18.


Multidrug resistant (MDR) cancer cells overexpressing P-glycoprotein (P-gp) display variations in invasive and metastatic behavior. We aimed to clarify the mechanism(s) underlying this observation and transfected vectors carrying CD147, a glycoprotein enriched on the surface of tumor cells that stimulates the production of matrix metalloproteinases (MMPs), and specific shCD147 into MCF7 and MCF7/Adr cells, respectively. Using quantitative real-time polymerase chain reaction and Western blot, we found that overexpression of CD147 in MCF7 cells up-regulated MDR1, MMP2, and MMP9 on both transcription and expression levels, which promoted tumor cells metastasis and conferred them multidrug resistance to P-gp substrate drugs, as determined by in vitro invasion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. On the other hand, silencing of CD147 in MCF7/Adr cells led to the opposite effect. Moreover, Erk1/2 in CD147-overexpressing clones were observed to be highly activate and after treatment with U0126, an Erk1/2-specific inhibitor, the expression of MDR1, MMP2 and MMP9 were decreased significantly. Thus, CD147 may assume a dual role, since it had intrinsic stimulative effects on tumor invasion in vitro as well as increasing resistance to P-gp substrate drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • Antigens, CD / genetics
  • Antigens, CD / physiology
  • Antineoplastic Agents / toxicity
  • Basigin / genetics
  • Basigin / physiology*
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • DNA Primers
  • Drug Resistance, Multiple*
  • Female
  • Gene Expression Regulation
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antigens, CD
  • Antineoplastic Agents
  • DNA Primers
  • RNA, Messenger
  • RNA, Neoplasm
  • Basigin
  • Matrix Metalloproteinases