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Yonsei medical journal v.51 no.5, 2010년, pp.708 - 716   SCIE
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Pseudomonas aeruginosa Exotoxin A Reduces Chemoresistance of Oral Squamous Carcinoma Cell via Inhibition of Heat Shock Proteins 70 (HSP70)

Park, Sang Rye    (Department of Oral Anatomy, School of Dentistry, Research Institute for Oral Biotechnology, Pusan National University, Yangsan, Korea.   ); Lee, Kyoung Duk    (Department of Oral Anatomy, School of Dentistry, Research Institute for Oral Biotechnology, Pusan National University, Yangsan, Korea.   ); Kim, Uk Kyu    (Department of Oral and Maxillofacial Surgery, School of Dentistry, Research Institute for Oral Biotechnology, Pusan National University, Yangsan, Korea.   ); Gil, Young Gi    (Department of Anatomy, College of Medicine, Kosin University, Busan, Korea.   ); Oh, Kyu Seon    (Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.   ); Park, Bong Soo    (Department of Oral Anatomy, School of Dentistry, Research Institute for Oral Biotechnology, Pusan National University, Yangsan, Korea.   ); Kim, Gyoo Cheon    (Department of Oral Anatomy, School of Dentistry, Research Institute for Oral Biotechnology, Pusan National University, Yangsan, Korea.  );
  • 초록

    Purpose Oral squamous carcinoma (OSCC) cells exhibit resistance to chemotherapeutic agent-mediated apoptosis in the late stage of malignancy. Increased levels of heat shock proteins 70 (HSP70) in cancer cells are known to confer resistance to apoptosis. Since recent advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers, we investigated the effect of Pseudomonas aeruginosa exotoxin A (PEA) on HSP70 expression and induction of apoptosis in chemoresistant OSCC cell line (YD-9). Materials and Methods The apoptotic effect of PEA on chemoresistant YD-9 cells was confirmed by MTT, Hoechst and TUNEL stains, DNA electrophoresis, and Western blot analysis. Results While YD-9 cells showed high resistance to chemotherapeutic agents such as etoposide and 5-fluorouraci (5-FU), HSP70 antisense oligonucelotides sensitized chemoresistant YD-9 cells to etoposide and 5-FU. On the other hand, PEA significantly decreased the viability of YD-9 cells by deteriorating the HSP70-relating protecting system through inhibition of HSP70 expression and inducing apoptosis in YD-9 cells. Apoptotic manifestations were evidenced by changes in nuclear morphology, generation of DNA fragmentation, and activation of caspases. While p53, p21, and E2F-1 were upregulated, cdk2 and cyclin B were downregulated by PEA treatment, suggesting that PEA caused cell cycle arrest at the G2/M checkpoint. Conclusion Therefore, these results indicate that PEA reduced the chemoresistance through inhibition of HSP70 expression and also induced apoptosis in chemoresistant YD-9 cells.


  • 주제어

    Pseudomonas aeruginosa exotoxin A .   chemoresistance .   oral squamous cell carcinoma cells .   heat shock protein 70 .   apoptosis.  

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