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Tumor Biology

, Volume 37, Issue 2, pp 2673–2682 | Cite as

CIP2A is associated with multidrug resistance in cervical adenocarcinoma by a P-glycoprotein pathway

  • Juan Liu
  • Meng Wang
  • Xiaoli Zhang
  • Qingwei Wang
  • Mei Qi
  • Jing Hu
  • Zhiqiang Zhou
  • Chunyan Zhang
  • Weifang Zhang
  • Weiming Zhao
  • Xiao Wang
Original Article

Abstract

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein. Here, we investigated its role in the formation of multidrug resistance (MDR) of cervical adenocarcinoma in vitro and in vivo. MTT assay showed that knockdown of CIP2A expression increased the drug sensitivity of HeLa and Dox-resistant HeLa cells (HeLa-Dox) to doxorubicin, cisplatin, and paclitaxel significantly, while overexpression of CIP2A decreased the sensitivity of HeLa cells to chemo-drugs dramatically. When treated with different chemotherapeutics, CIP2A and P-glycoprotein (P-gp) protein levels were increased in HeLa cells simultaneously. In accordance with it, knockdown or overexpression of CIP2A expression inhibited or increased the P-gp expression in the transcription level separately. The effects of CIP2A on P-gp expression was achieved partly through its regulation on the transcription factor E2F1. Moreover, the interference of CIP2A could decrease the P-gp protein activity elucidated by Rhodamine 123 (Rh123) efflux assay in HeLa and HeLa/Dox cells. In the in vivo level, confocal microscopy data demonstrated the strong co-localization of CIP2A and P-gp protein in HeLa cells, and CIP2A protein expression was significantly associated with that of P-gp in cervical adenocarcinoma tissues. Thus, CIP2A is involved in regulating multidrug resistance of cervical adenocarcinoma upon chemotherapy by enhancing P-gp expression through E2F1. CIP2A may be an attractive target in anticancer strategies to improve the effect of chemotherapy in cervical adenocarcinoma.

Keywords

Cervical cancer Cancerous inhibitor of protein phosphatase 2A Chemotherapy Multidrug resistance P-glycoprotein 

Notes

Acknowledgments

This research was supported by the National Natural Science Foundation of China (grant no. 81000733), Shandong Province Natural Science Foundation (grant nos. ZR2011HQ036 and ZR2012HM031), and the National Natural Science Foundation of China (grant nos. 81101259 and 81472552).

Conflicts of interest

None

Supplementary material

13277_2015_4032_MOESM1_ESM.doc (228 kb)
ESM 1 (DOC 228 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Juan Liu
    • 2
  • Meng Wang
    • 3
  • Xiaoli Zhang
    • 2
  • Qingwei Wang
    • 3
  • Mei Qi
    • 2
  • Jing Hu
    • 1
  • Zhiqiang Zhou
    • 1
  • Chunyan Zhang
    • 1
  • Weifang Zhang
    • 2
  • Weiming Zhao
    • 2
  • Xiao Wang
    • 1
  1. 1.Department of Pathology, School of MedicineShandong UniversityJinanPeople’s Republic of China
  2. 2.Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of MedicineShandong UniversityJinanPeople’s Republic of China
  3. 3.Department of Radiation OncologyQi Lu hospital of Shandong UniversityJinanPeople’s Republic of China

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