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. 2021 Apr 9;11(4):479.
doi: 10.3390/brainsci11040479.

Chewing Behavior Attenuates the Tumor Progression-Enhancing Effects of Psychological Stress in a Breast Cancer Model Mouse

Qian Zhou  1 , Masahisa Katano  2 , Jia-He Zhang  1 , Xiao Liu  1 , Ke-Yong Wang  3 , Mitsuo Iinuma  2 , Kin-Ya Kubo  4 , Kagaku Azuma  1
Affiliations

Chewing Behavior Attenuates the Tumor Progression-Enhancing Effects of Psychological Stress in a Breast Cancer Model Mouse

Qian Zhou et al. Brain Sci. .

Abstract

We examined whether chewing behavior affects the tumor progression-enhancing impact of psychological stress. Human breast cancer cell line (MDA-MB-231) cells were inoculated into the mammary fat pads of athymic nude mice. The mice were assigned randomly to control, stress, and stress+chewing groups. Psychological stress was created by keeping mice in a transparent restraint cylinder for 45 min, three times a day, for 35 days after cell inoculation. Animals in the stress+chewing group were provided with a wooden stick for chewing on during the psychological stress period. Chewing behavior remarkably inhibited the tumor growth accelerated by the psychological stress. Immunohistochemical and Western blot findings revealed that chewing behavior during psychological stress markedly suppressed tumor angiogenesis and cell proliferation. In addition, chewing behavior decreased serum glucocorticoid levels and expressions of glucocorticoid and β2-adrenergic receptors in tumors. Chewing behavior decreased expressions of inducible nitric oxide synthase and 4-hydroxynonenal, and increased expression of superoxide dismutase 2 in tumors. Our findings suggest that chewing behavior could ameliorate the enhancing effects of psychological stress on the progression of breast cancer, at least partially, through modulating stress hormones and their receptors, and the subsequent signaling pathways involving reactive oxygen and nitrogen species.

Keywords: breast cancer; chewing behavior; glucocorticoid; oxidative stress; psychological stress; β2-adrenergic receptor.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1
Chewing behavior during psychological stress inhibited tumor growth. (A) Mouse body weight growth curves. (B) Tumor growth curves. (C) Representative photograph of tumors after dissection. (D) Tumor weight on day 35 after inoculation. (** p < 0.01 vs. control group, ## p < 0.01 vs. stress group, n = 9/group). All data are expressed as mean ± SEM.
Figure 2
Figure 2
Chewing behavior during psychological stress alleviated tumor angiogenesis and proliferation. (A) Representative photographs of CD31-positive cells and Ki67-positive cells in the tumor. (B) The percentage of microvessel area in the tumor. (C) The percentage of Ki67-positive cells in the tumor. (D) The expression level of CD31 in the tumor. (E) The expression level of Ki67 in the tumor. (** p< 0.01 vs. control group, ## p < 0.01 vs. stress group, n = 9/group). All data are expressed as mean ± SEM.
Figure 3
Figure 3
Chewing behavior during psychological stress decreased serum glucocorticoid levels and expression of GR in the tumor. (A) Serum glucocorticoid levels. (B) The expression level of GR protein in the tumor. (C) Percentage of GR-positive cells in the tumor. (D) Representative photographs of GR-positive cells in the tumor. (** p < 0.01 vs. control group, ## p < 0.01 vs. stress group, n = 9/group). All data are expressed as mean ± SEM.
Figure 4
Figure 4
Chewing behavior during psychological stress decreased the expression of β2AR in the tumor. (A) Representative photographs of β2AR-positive cells in the tumor. (B) The percentage of β2AR-positive cells in the tumor. (C) The expression level of β2AR protein in the tumor. (** p < 0.01 vs. control group, ## p < 0.01 vs. stress group, n = 9/group). All data are expressed as mean ± SEM.
Figure 5
Figure 5
Chewing behavior during psychological stress improved oxidative stress in the tumor. (A) The expression level of iNOS protein in the tumor. (B) The expression level of 4HNE protein in the tumor. (C) The expression level of SOD2 protein in the tumor (** p < 0.01 vs. control group, ## p < 0.01 vs. stress group, n = 9/group). All data are expressed as mean ± SEM.
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References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Momenimovahed Z., Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer. 2019;11:151–164. doi: 10.2147/BCTT.S176070. - DOI - PMC - PubMed
    1. Narod S.A., Foulkes W.D. BRCA1 and BRCA2: 1994 and beyond. Nat. Rev. Cancer. 2004;4:665–676. doi: 10.1038/nrc1431. - DOI - PubMed
    1. Cui B., Luo Y., Tian P., Peng F., Lu J., Yang Y., Su Q., Liu B., Yu J., Luo X., et al. Stress-induced epinephrine enhances lactate dehydrogenase A and promotes breast cancer stem-like cells. J. Clin. Investig. 2019;129:1030–1046. doi: 10.1172/JCI121685. - DOI - PMC - PubMed
    1. Le C.P., Nowell C.J., Kim-Fuchs C., Botteri E., Hiller J.G., Ismail H., Pimentel M.A., Chai M.G., Karnezis T., Rotmensz N., et al. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat. Commun. 2016;7:10634. doi: 10.1038/ncomms10634. - DOI - PMC - PubMed

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