Abnormal Tumor‐Associated Molecules Expression in both Depression Patients and Chronic Stressed Mice
Authors: Xu Feng , Ren Yu 
Published: June 2021

Objective

Persistent activation of the hypothalamic‐pituitary‐adrenal (HPA) axis impairs the immune response. Chronic stress is associated with decreased cytotoxic T‐cells and NK cells activities that affect the immune surveillance of tumors. However, whether chronic stress affects tumor‐associated gene expression is not clear.

Methods

(1) Informed consent was obtained from all subjects. HAMD scale was used to assess mental health volunteers and depression patients with > one negative life events over 1 year. Blood samples were drawn and whole blood gene chip expression profiles were analyzed. Differential expressed gene was verified by RT‐PCR. (2) Normal C57 mice were randomized into 6 groups, (A) blank control, (B) depression, (C) Lewis lung cancer control, (D) Lewis lung cancer depression, (E) Lewis lung cancer + fluoxetine treatment, and (F) Lewis lung cancer depression + fluoxetine treatment. Mice in the B, D, and F groups were given chronic stress for 8 weeks, and mice in the other groups were fed normally. The depression‐behavioral mice were evaluated with behavioral analysis and sucrose preference test. After 8 weeks of chronic stress treatment, mice in groups C, D, E, and F were inoculated with LLC lung cancer tumor cells. Mice in Group E and F were given fluoxetine on the third day after tumor‐inoculation, and mice in Group A, B, C, and D were given normal saline. The body weight was measured regularly. After 14 days of continuous fluoxetine administration all mice were sacrificed and tumors were excised. The volume and weight of tumors were measured. The expression of tumor‐associated gene mRNAs and protein in the liver of mice was determined by RT‐PCR and Western blotting assay.

Results

(1) Compared with normal mental healthy volunteers, a total of 18,853 genes in the whole blood of depression patients showed significant differences. Four tumor‐associated genes mRNA (PTTG1, OSBPL5, AATF, TNFRSF18) were screened out and their up‐regulation was confirmed by RT‐PCR. (2) The above 4 mRNA tumor‐associated genes in the liver of chronic stress‐induced depression‐behavioral mice (Group B) were highly expressed compared with mice in Group A, which was consistent with the results in whole blood gene expression in depression patients. The expression of the 4 mRNAs in Group F mice administered with fluoxetine was decreased in different extent. Compared with the mice in Group C, the tumor weight and volume of mice in Group D was significantly increased; while significant decreased in mice in Group E. Compared with mice in Group D, mice tumor weight and volume in Group F were significantly reduced.

Conclusion

The expression of tumor‐related genes in depression patient and in chronic stress‐induced depression‐behavioral mice has increased, suggesting that depression and chronic stress can promote the development of tumors. The antidepressant fluoxetine can effectively slow the tumor growth, showing a certain anti‐tumor activity, and its mechanism may be related to the inhibition of tumor‐related gene expression.

Support or Funding Information

The work was supported by Shanghai Natural Science Foundation (14ZR1434700) and Shanghai Municipal Science Committee (16411973200).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.