Cai Song, Ph.D.

Research Institute for Marine Drug and Nutrition, and Marine Medical Centre, Shenzhen Institute, Guangdong Ocean University, P. R. China.

Epidemiological investigations reported that depression was positively correlated with the high incidence of cancers and low survival rate. As a trigger of depression, chronic stress can 1) stimulate the hypothalamic-pituitary-adrenal (HPA) axis to secrete glucocorticoids; 2) activate glial cells and trigger neuroinflammation, but suppress neurotrophic function and 3) increase oxidative stress in the brain. These changes can induce dysfunction of neurotransmission and neuronal apoptosis, eventually leading to depression. However, the relationship between stress and cancer development is unclear. The present study explored how chronic unpredictable and mild stress (CUMS) promotes the expression of lung cancer related factors in A/J mice after exposure to smoke. CUMS and smoke exposure (SE) were performed on A/J mice for 8 weeks. Then, animal behavior in sucrose preference (SP) and forced swimming (FS) were tested. Animal blood corticosterone concentration, peripheral inflammatory responses and lung cancer-related factors, as well as the expression of amygdala neurotrophic factors and receptors, and apoptosis genes were measured.

Compared to the control, CUMS mice showed depression-like behaviors, such as increased anhedonia in the SP and immobility time in the FS, which were deteriorated in CUMS+SE mice. Parallely, CUMS+SE mice showed much higher corticosterone level than that in CUMS group. CUMS alone decreased lymphocyte proliferation and increased the expression of lung cancer-related factor HSP-90α and concentrations of interleukin (IL)-1b, IL-6, IL-8 and IL-12 when compared to the control. However, further increased HSP-90α, but decreased TNF-a and IL-10 concentrations in CUMS+SE mice was found when compared to CUMS or SE group alone. In the amygdale, mRNA and protein expressions of miroglia CD11b and P75 receptor were increased, while NGF were decreased in CUMS mice compared with the control. However, in CUMS+SE mice, suppressed both microglial and astrocyte markers, down-regulation of both BDNF and NGF, their receptors, as well as decreased expression of anti-apoptosis gene Bcl2 were found. The present study demonstrated that 1) CUMS could induce depression-like changes and enhance the expression of lung cancer-related factors; 2) CUMS and SE could synergistically suppress cellular immune function, but enhance humoral immunity; 3) the synergitic effects between CUMS and SE can induce more severe depression-like symptoms. These results suggest that chronic stress can synergy lung cancer development, while cancer development may deteriorate stress-induced depressive symptoms.