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17β-Estradiol inhibits prostaglandin E2-induced COX-2 expressions and cell migration by suppressing Akt and ERK1/2 signaling pathways in human LoVo colon cancer cells

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Abstract

Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17β-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2)-induced cellular motility in human colon cancer cells. Upregulation of cyclooxygenase-2 (COX-2) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), or QNZ (NFκB inhibitor), we found that PGE2 treatment increases COX-2 via Akt and ERK1/2 pathways, thus promoting cellular motility in human LoVo cancer cells. We further observed that 17β-estradiol treatment inhibits PGE2-induced COX-2 expression and cellular motility via suppressing activation of Akt and ERK1/2 in human LoVo cancer cells. Collectively, these results suggest that 17β-estradiol treatment dramatically inhibits PGE2-induced progression of human LoVo colon cancer cells.

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Abbreviations

E2:

17β-Estradiol

PGE2:

Prostaglandin E2

ERK:

Extracellular signal regulated kinase

p38 MAPK:

p38 Mitogen-activated protein kinase

JNK:

c-Jun N-terminal kinase

NF-κB:

Nuclear factor κ B

PI3-K:

Phosphatidylinositol 3-kinase

PKB:

Protein kinase B

DMEM:

Dulbecco’s modified Eagle’s medium

QNZ:

6-Amino-4-(4-phenoxyphenylethylamino) quinazoline

ECM:

Extracellular matrix

PBS:

Phosphate-buffered saline

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Acknowledgments

This study is supported by Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH99-TD-B-111-004) and in part by Taiwan Department of Health Cancer Research Center of Excellence (DOH99-TD-C-111-005).

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Authors and Affiliations

  1. College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, 404, Taiwan

    Tung-Yuan Lai

  2. Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan

    Tung-Yuan Lai

  3. Division of Medical Technology, Department of Internal Medicine, Armed-Force, Taichung General Hospital, Taichung, Taiwan

    Li-Mien Chen

  4. Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan

    Jing-Ying Lin

  5. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

    Bor-Show Tzang

  6. Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

    James A. Lin & Chih-Yang Huang

  7. Department of Healthcare Administration, Asia University, Taichung, Taiwan

    Chang-Hai Tsai

  8. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan

    Yueh-Min Lin

  9. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan

    Chih-Yang Huang & Chung-Jung Liu

  10. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

    Chih-Yang Huang

  11. Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan

    Hsi-Hsien Hsu

  12. Mackay Medicine, Nursing and Management College, Taipei, Taiwan

    Hsi-Hsien Hsu

Authors
  1. Tung-Yuan Lai
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  2. Li-Mien Chen
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  5. James A. Lin
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  7. Yueh-Min Lin
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  8. Chih-Yang Huang
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  9. Chung-Jung Liu
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  10. Hsi-Hsien Hsu
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Corresponding author

Correspondence to Hsi-Hsien Hsu.

Additional information

Chih-Yang Huang, Chung-Jung Liu, and Hsi-Hsien Hsu contributed equally to this article.

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Lai, TY., Chen, LM., Lin, JY. et al. 17β-Estradiol inhibits prostaglandin E2-induced COX-2 expressions and cell migration by suppressing Akt and ERK1/2 signaling pathways in human LoVo colon cancer cells. Mol Cell Biochem 342, 63–70 (2010). https://doi.org/10.1007/s11010-010-0469-7

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  • DOI: https://doi.org/10.1007/s11010-010-0469-7

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