Cancer Res Treat.  2019 Oct;51(4):1620-1631. 10.4143/crt.2018.340.

Low Doses of Nonylphenol Promote Growth of Colon Cancer Cells through Activation of ERK1/2 via G Protein‒Coupled Receptor 30

Affiliations
  • 1Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, China. yangxuefeng923@163.com

Abstract

PURPOSE
Nonylphenol (NP) is an endocrine disruptor found in products such as cleaners, plastics, and detergents. It exerts actions similar to endogenous 17β-estradiol (E2) and is reported to influence various cancers. However, its role in colon cancer remains elusive.
MATERIALS AND METHODS
Colon cancer cell lines COLO 205 and SW480 were employed in our study. The cells were treated with NP or E2 followed by measurement of apoptosis and proliferation using flow cytometry and MTT assays, respectively. G protein-coupled estrogen receptor 30 (GPR30) expression was visualized using immunofluorescence and Western blot. To investigate the underlying mechanism, the expression levels of GPR30, p-protein kinase A (PKA), c-myc, cyclin D1, and ERK1/2 were analyzed using Western blot. Meanwhile, the GPR30 antagonist G15 was utilized to validate the role of GPR30 in colon cancer progression. Finally, the effect of a GPR30 inhibitor on tumor growth was determined in vivo using tumor xenograft mouse models.
RESULTS
NP facilitated the proliferation of colon cancer cells and induced apoptosis failure in vitro. Western blot revealed increased GPR30 expression levels in response to NP treatment. Cyclin D1, p-PKA, c-myc, and proliferating cell nuclear antigen, proteins that regulate the cell cycle, were all upregulated by NP, and NP-mediated ERK1/2 activation and subsequent cell proliferation were abrogated by the GPR30 inhibitor G15. Moreover, colon cancer mice that received G15 administration demonstrated impaired tumor growth in vivo.
CONCLUSION
Low dose NP promotes the growth of colon tumors through GPR30-mediated activation of ERK1/2 signaling.

Keyword

Nonylphenol; GPR30; Colon neoplasms; ERK1/2; Cell proliferation; Cyclin D1

MeSH Terms

Animals
Apoptosis
Blotting, Western
Cell Cycle
Cell Line
Cell Proliferation
Colon*
Colonic Neoplasms*
Cyclin D1
Detergents
Estrogens
Flow Cytometry
Fluorescent Antibody Technique
Heterografts
In Vitro Techniques
Mice
Phosphotransferases
Plastics
Proliferating Cell Nuclear Antigen
Cyclin D1
Detergents
Estrogens
Phosphotransferases
Plastics
Proliferating Cell Nuclear Antigen
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