Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Sensitization of Cervical Carcinoma Cells to Paclitaxel by an IPP5 Active Mutant

  • Zeng, Qi-Yan (Department of Biochemistry and Molecular Biology, Guangxi Medical University) ;
  • Huang, Yu (Clinical Laboratory Center, Nanfang Hospital) ;
  • Zeng, Lin-Jie (Department of Orthopaedics, Orthopaedics Hospital) ;
  • Huang, Min (School of Preclinical Medicine, Guangxi Medical University) ;
  • Huang, Yong-Qi (Department of Biochemistry and Molecular Biology, Guangxi Medical University) ;
  • Zhu, Qi-Fang (Department of Biochemistry and Molecular Biology, Guangxi Medical University)
  • Published : 2014.10.23
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Abstract

Paclitaxel is one of the best anticancer agents that has been isolated from plants, but its major disadvantage is its dose-limiting toxicity. In this study, we obtained evidence that the active mutant IPP5 ($8-60hIPP5^m$), the latest member of the inhibitory molecules for protein phosphatase 1, sensitizes human cervix carcinoma cells HeLa more efficiently to the therapeutic effects of paclitaxel. The combination of $8-60hIPP5^m$ with paclitaxel augmented anticancer effects as compared to paclitaxel alone as evidenced by reduced DNA synthesis and increased cytotoxicity in HeLa cells. Furthermore, our results revealed that $8-60hIPP5^m$ enhances paclitaxel-induced G2/M arrest and apoptosis, and augments paclitaxel-induced activation of caspases and release of cytochrome C. Evaluation of signaling pathways indicated that this synergism was in part related to downregulation of NF-${\kappa}B$ activation and serine/threonine kinase Akt pathways. We noted that $8-60hIPP5^m$ downregulated the paclitaxel-induced NF-${\kappa}B$ activation, $I{\kappa}B{\alpha}$ degradation, PI3-K activity and phosphorylation of the serine/threonine kinase Akt, a survival signal which in many instances is regulated by NF-${\kappa}B$. Together, our observations indicate that paclitaxel in combination with $8-60hIPP5^m$ may provide a therapeutic advantage for the treatment of human cervical carcinoma.

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References

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