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Volume 10 Journal of Cancer Science & Therapy
ISSN: 1948-5956 Breast Cancer 2018
May 10-11, 2018
May 10-11, 2018 | Frankfurt, Germany
7th World Congress on Breast Cancer
Melatonin enhances chemosensitivity of human endothelial and breast cancer cells by regulating
genes involved in angiogenesis
Alicia González González, Alicia González, Carolina Alonso González, Carlos Martínez Campa, Javier Menéndez Menéndez and Samuel Cos
1University of Cantabria, Spain
2Instituto de Investigación Valdecilla, Spain
Endothelial cells represent one of the critical cellular elements in tumor microenvironment playing a crucial role in the
growth and progression of cancer through controlling angiogenesis. Enhancing the chemosensitivity of cancer cells is
one of the most important goals in clinical chemotherapy. Melatoanin exerts oncostatic activity in breast cancer through
antiangiogenic actions. Vascular endothelial growth factor (VEGF) produced from tumor cells is essential for the expansion of
breast cancer. The angiopoietin/Tie-2 family play an important role in regulating vessel stability. Several studies emphasize the
complementary and coordinated roles of angiopoietin-2 and VEGF during angiogenesis. Thus, the aim of the present study was
to investigate whether melatonin sensitizes endothelial cells to chemotherapy by regulating angiogenesis. To accomplish this
we used human umbilical vein endothelial cells (HUVEC) or cocultures of HUVEC cells with MCF-7 cells. Cell proliferation
was measured by the MTT method. We selected different genes which were modulated by melatonin from an array of genes
involved with the process of angiogenesis. Their expression was analyzed by RT-PCR. The migration of HUVECs was measured
by the Wound Healing Assay and tubulogenesis studies were performed in a tubulogenesis multiplate system in vitro. Only
the presence of malignant epithelial cells in the cocultures altered proliferation, and stimulated ANG-1, ANG-2 and VEGF
expression and decreased Tie2 expression in endothelial cells. Melatonin 1 mM added to the coculture counteracted this effect
and reduced Ang-1, Ang-2 and VEGF expression and increased Tie-2 expression. In addition, vinorrelbine and docetaxel
decreased cell proliferation and melatonin led to a significantly greater decrease. Furthermore, it is important to point out
that chemotherapy increases the expression of genes involved in angiogenesis such as VEGF, ANG1, ANG2, FGFR3, NOS3 or
MMP14, and melatonin pretreatment 1 mM led to a significantly decrease. Furthermore, the migration of endothelial cells
and the tube formation were reduced with the chemotherapy and melatonin pretreatment resulted in a significantly higher
reduction. All these results suggest that melatonin could exert a cooperative enhancement of chemosensitivity associated
with the modulation of angiogenesis. Therefore, melatonin could represent a new and promising therapeutic approach to the
treatment of breast cancer.
Biography
Alicia González González is a PhD student from Cantabria University School of Medicine. Currently, she is involved in Breast Cancer research and Melatonin, specifically
in the sensitizing effects of melatonin to chemotherapy and radiotherapy for its antiangiogenic and antiadipogenic actions. She has published three papers and she has
presented her work in five international conferences.
Alicia González González et al., J Cancer Sci Ther 2018, Volume 10
DOI: 10.4172/1948-5956-C2-126