In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 4 ( 2022-4-12), p. e0266073-
Kurzfassung:
Obesity is associated with an increased incidence and aggressiveness of breast cancer and is estimated to increment the development of this tumor by 50 to 86%. These associations are driven, in part, by changes in the serum molecules. Epidemiological studies have reported that Metformin reduces the incidence of obesity-associated cancer, probably by regulating the metabolic state. In this study, we evaluated in a breast cancer in-vitro model the activation of the IR-β/Akt/p70S6K pathway by exposure to human sera with different metabolic and hormonal characteristics. Furthermore, we evaluated the effect of brief Metformin treatment on sera of obese postmenopausal women and its impact on Akt and NF-κB activation. We demonstrated that MCF-7 cells represent a robust cellular model to differentiate Akt pathway activation influenced by the stimulation with sera from obese women, resulting in increased cell viability rates compared to cells stimulated with sera from normal-weight women. In particular, stimulation with sera from postmenopausal obese women showed an increase in the phosphorylation of IR-β and Akt proteins. These effects were reversed after exposure of MCF-7 cells to sera from postmenopausal obese women with insulin resistance with Metformin treatment. Whereas sera from women without insulin resistance affected NF-κB regulation. We further demonstrated that sera from post-Metformin obese women induced an increase in p38 phosphorylation, independent of insulin resistance. Our results suggest a possible mechanism in which obesity-mediated serum molecules could enhance the development of luminal A-breast cancer by increasing Akt activation. Further, we provided evidence that the phenomenon was reversed by Metformin treatment in a subgroup of women.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0266073
DOI:
10.1371/journal.pone.0266073.g001
DOI:
10.1371/journal.pone.0266073.g002
DOI:
10.1371/journal.pone.0266073.g003
DOI:
10.1371/journal.pone.0266073.g004
DOI:
10.1371/journal.pone.0266073.g005
DOI:
10.1371/journal.pone.0266073.g006
DOI:
10.1371/journal.pone.0266073.t001
DOI:
10.1371/journal.pone.0266073.t002
DOI:
10.1371/journal.pone.0266073.s001
DOI:
10.1371/journal.pone.0266073.s002
DOI:
10.1371/journal.pone.0266073.s003
DOI:
10.1371/journal.pone.0266073.s004
DOI:
10.1371/journal.pone.0266073.s005
DOI:
10.1371/journal.pone.0266073.s006
DOI:
10.1371/journal.pone.0266073.s007
DOI:
10.1371/journal.pone.0266073.s008
DOI:
10.1371/journal.pone.0266073.s009
DOI:
10.1371/journal.pone.0266073.s010
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2267670-3
