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

Qing Quan Li, Wen Juan Wang, Jing Da Xu, Xi Xi Cao, Qi Chen, Jin Ming Yang, Zu De Xu

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1064-1069
Number of pages6
JournalCancer Science
Volume98
Issue number7
DOIs
StatePublished - Jul 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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