P-89 Function and regulation of insulin-like growth factor binding protein-2 and -3 in ovarian cancer cell models

Resveratrol (trans-3,4,5-trihydroxystilbene; RES) was adopted in this study as a novel phytoestrogen displaying antioxidant, antiinflammatory, and anticancer effects. In this study, we evaluated the inhibitory effect of RES on the cell growth induced by 17β-oestradiol (E2), a typical oestrogen, and bisphenol A (BPA), an endocrine-disrupting chemical (EDC) in BG-1 ovarian cancer cells expressing oestrogen receptors (ER) through down-regulating oestrogen receptor α (ERa) and insulin-like growth factor-1 receptor (IGF-1R). The EDC and oestrogen appear to promote the development of the oestrogen-dependent cancers. Thus, we need to develop therapeutic methods for EDC-dependent cancers. In in vitro experiments, we examined the cell viability and mRNA expression of ERa ± IGF-1R genes following the treatments with E2 or BPA in the presence or absence of RES or ICI 182 780, an ER antagonist, by MTT assay and RT-PCR, respectively. We also examined the protein level of ERa, phosphorylated insulin receptor substrate-1 (IRS-1), phosphorylated Akt1/2/3, p21, and cyclin D1 by Western blot analysis. Treatment with E2 or BPA remarkably increased the growth of BG-1 ovarian cancer cells, and their enhanced cell growth appeared to be mediated by ERa. In addition, the treatment of BG-1 ovarian cancer cells with E2 or BPA resulted in an increase in ERa and IGF-1R gene expressions. However, co-treatment of RES reversed E2- or BPA-induced ovarian cancer cell growth and mRNA expressions of ERa and IGF-1R. The protein levels of phosphorylated IRS-1 and Akt were upregulated by E2 or BPA, whereas these levels were downregulated by co-treatment of RES in the presence of E2 or BPA. Taken together, these results indicate that RES may effectively inhibit ovarian cancer cell growth via downregulating cross-talk between ERa and IGF-1R. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of Korea government (no. 2011-0015385).

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Apelin abrogates the stimulatory effects of 17β-estradiol and insulin-like growth factor-1 on proliferation of epithelial and granulosa ovarian cancer cell lines via crosstalk between APLNR and ERα/IGF1R

Molecular Biology Reports ◽

10.1007/s11033-019-05073-2 ◽

2019 ◽

Vol 46 (6) ◽

pp. 6325-6338

Author(s):

Marta Hoffmann ◽

Justyna Gogola ◽

Anna Ptak

Keyword(s):

Ovarian Cancer ◽

Growth Factor ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

The Body ◽

Insulin Like Growth Factor ◽

Ovarian Cancer Cell Lines ◽

17Β Estradiol

Abstract Apelin and chemerin are adipocytokines that play important roles in many physiological and pathological processes throughout the body. Our previous study demonstrated that these two adipokines are expressed and secreted by epithelial and granulosa cancer cell lines. 17β-estradiol (E2) and insulin-like growth factor-1 (IGF-1) are important regulators of ovarian functions, and their roles are well known. This study investigated whether apelin and chemerin regulate proliferation and apoptosis of epithelial (OVCAR-3) and granulosa (COV434) ovarian cancer cell lines by interacting with E2 and IGF-1. Apelin and chemerin did not affect caspase-3 activation in either cell line. However, apelin abrogated the stimulatory effects of E2 on proliferation of OVCAR-3 cells and of IGF-1 on proliferation of COV434 cells independently of ERK1/2 and PI3K via crosstalk of apelin receptor with estrogen receptor alpha and IGF-1 receptor, respectively.

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The Prognostic Values of the Insulin-Like Growth Factor Binding Protein Family in Ovarian Cancer

BioMed Research International ◽

10.1155/2020/7658782 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Ruoyi Zheng ◽

Wenming Chen ◽

Weiting Xia ◽

Jingyu Zheng ◽

Qing Zhou

Keyword(s):

Ovarian Cancer ◽

Growth Factor ◽

Protein Expression ◽

Mrna Expression ◽

Binding Protein ◽

Progression Free Survival ◽

Prognostic Impact ◽

Mrna Levels ◽

Insulin Like Growth Factor ◽

Factor Binding

Purpose. To assess the expression of insulin-like growth factor binding protein (IGFBP) family and its prognostic impact in ovarian cancer (OC) patients. Materials and Methods. The mRNA expression and protein expression of individual IGFBPs in healthy ovarian samples and OC tissues were explored through Oncomine, Gene Expression Profiling Interactive Analysis, and Human Protein Atlas database. Additionally, the prognostic values of the six IGFBP members in patients with OC were evaluated by Kaplan-Meier plotter. Results. IGFBP2 and IGFBP4 mRNA expression were remarkably upregulated in patients with OC. To be specific, the mRNA expression of IGFBP2 was upregulated in patients with serous ovarian cancer (SOC), while IGFBP1/3/4/5/6 mRNA levels were downregulated. In addition, the IGFBP4 protein expression was upregulated in SOC, and the IGFBP6 protein expression was upregulated in both of SOC and endometrioid ovarian cancer (EOC) tissues. High IGFBP1 mRNA levels showed favorable overall survival (OS) and progression-free survival (PFS) in all OC. Meanwhile, increased IGFBP5/6 mRNA levels revealed worsen OS and PFS in all OC patients. IGFBP4/6 mRNA levels predicted unfavorable OS and PFS only in SOC patients. Moreover, the aberrant mRNA expression of IGFBP1/2/4/5/6 was correlated with significantly prognosis in patients receiving different chemotherapeutic regimens. Conclusion. This study indicates that the IGFBP family reveals distinct prognosis in patients with OC. IGFBP1/2/4/5/6 are useful prognostic predictors for chemotherapeutic effect in OC patients, and IGFBP2/4 are potential tumor markers for the diagnosis of OC.

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