Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors

Gayathri Chadalapaka, Indira Jutooru, Sandeep Sreevalsan, Satya Pathi, Kyounghyun Kim, Candy Chen, Lisa Crose, Corinne Linardic, Stephen Safe

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 are highly expressed in rhabdomyosarcoma (RMS) cells. In tissue arrays of RMS tumor cores from 71 patients, 80% of RMS patients expressed high levels of Sp1 protein, whereas low expression of Sp1 was detected in normal muscle tissue. The non-steroidal anti-inflammatory drug (NSAID) tolfenamic acid (TA) inhibited growth and migration of RD and RH30 RMS cell lines and also inhibited tumor growth in vivo using a mouse xenograft (RH30 cells) model. The effects of TA were accompanied by downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes in RMS cells and tumors, and the role of Sp protein downregulation in mediating inhibition of RD and RH30 cell growth and migration was confirmed by individual and combined knockdown of Sp1, Sp3 and Sp4 proteins by RNA interference. TA treatment and Sp knockdown in RD and RH30 cells also showed that four genes that are emerging as individual drug targets for treating RMS, namely c-MET, insulin-like growth factor receptor (IGFR), PDGFRα and CXCR4, are also Sp-regulated genes. These results suggest that NSAIDs such as TA may have potential clinical efficacy in drug combinations for treating RMS patients.

Original languageEnglish (US)
Pages (from-to)795-806
Number of pages12
JournalInternational Journal of Cancer
Volume132
Issue number4
DOIs
StatePublished - Feb 15 2012

Keywords

  • RMS cells
  • Sp proteins
  • downregulation
  • tolfenamic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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