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Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells

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Abstract

Objective

Aquaporin (AQP) water channels are expressed in high-grade tumor cells of different tissue origins. Based on the involvement of AQPs in angiogenesis and cell migration as well as our previous studies which show that AQP3 is involved in human skin fibroblasts cell migration, in this study, we investigated whether AQP3 is expressed in cultured human ovarian cancer cell line CaOV3 cells, and whether AQP3 expression in these cells enhances cell migration and metastatic potential.

Methods

Cultured CaOV3 cells were treated with EGF and/or various reagents and subjected to cell migration assay by phagokinetic track mobility assay or biochemical analysis for expression or activation of proteins by SDS-PAGE/Western blot analysis.

Results

In this study, we demonstrate that AQP3 is expressed in CaOV3 cells. EGF induces CaOV3 migration and up-regulates AQP3 expression. EGF-induced cell migration is inhibited by specific AQP3 siRNA knockdown or AQP3 water transport inhibitor CuSO4 and NiCl2. We also find that curcumin, a well known anti-ovarian cancer drug, down-regulates AQP3 expression and reduces cell migration in CaOV3, and the effects of curcumin are mediated, at least in part, by its inhibitory effects on EGFR and downstream AKT/ERK activation.

Conclusions

Collectively, our results provide evidence for AQP3-facilitated ovarian cancer cell migration, suggesting a novel function for AQP3 expression in high-grade tumors. The results that curcumin inhibits EGF-induced up-regulation of AQP3 and cell migration, provide a new explanation for the anticancer potential of curcumin.

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Acknowledgments

This research was supported in part by a grant from NIH (P20 RR016457 from INBRE Program of the National Center for Research Resources), a grant for biomedical research from Rhode Island Foundation, a CAFR grant from Providence College, and a grant from Slater Center for Environmental Biotechnology, and a grant from National Natural Science Foundation (30471808).

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Authors and Affiliations

  1. Department of Biology, Providence College, 549 River Ave, Providence, RI, 02918, USA

    Chao Ji, Cong Cao, Shan Lu, Rebecca Kivlin, Ashley Amaral, Hui Yang & Yinsheng Wan

  2. Department of Immunology, Brown University, Providence, RI, 02903, USA

    Cong Cao & Wenming Chu

  3. Roger Williams Medical Center, Providence, RI, 02908, USA

    Nicola Kouttab

  4. Department of OB/GYN, Renji Hospital, Shanghai Jiaotong University, Shanghai, 200001, China

    Hui Yang & Wen Di

  5. Department of Dermatology, Nanjing Medical University, Nanjing, 2100029, China

    Chao Ji & Zhigang Bi

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  1. Chao Ji
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  2. Cong Cao
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  3. Shan Lu
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Correspondence to Yinsheng Wan.

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Ji, C., Cao, C., Lu, S. et al. Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells. Cancer Chemother Pharmacol 62, 857–865 (2008). https://doi.org/10.1007/s00280-007-0674-6

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  • DOI: https://doi.org/10.1007/s00280-007-0674-6

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