Chronic stress promoted the growth of ovarian carcinoma via increasing serum levels of norepinephrine and interleukin-10 and altering nm23 and NDRG1 expression in tumor tissues in nude mice

• Published in: BioScience Trends Vol. 7; no. 1; pp. 56 - 63
• Main Authors: Gao, Guolan, Sun, Jianling, Gao, Jun, Xiong, Lijuan, Yu, Liqun, Gao, Yulian
• Format: Journal Article
• Language: English
• Published: Japan International Research and Cooperation Association for Bio & Socio-Sciences Advancement 01.01.2013
• Subjects: Animals; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - pathology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Chronic stress; Female; Gene Expression Regulation, Neoplastic; Handling (Psychology); Humans; interleukin 10; Interleukin-10 - blood; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; NDRG1; nm23; NM23 Nucleoside Diphosphate Kinases - genetics; NM23 Nucleoside Diphosphate Kinases - metabolism; norepinephrine; Norepinephrine - blood; ovarian carcinoma; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Stress, Physiological; Transplantation, Heterologous - pathology
• ISSN: 1881-7815; 1881-7823
• DOI: 10.5582/bst.2013.v7.1.56

The current study aimed to examine the effects and underlying mechanisms of chronic psychological stress on the growth of ovarian carcinoma. Human ovarian carcinoma cells SKOV-3 were subcutaneously inoculated into nude mice to establish an ectopic mouse model. The animals were experimentally stressed 6 h daily for a total of 42 days with a physical restraint system. We examined the effects of stress on the growth of tumor cells that were inoculated 7 days after the initiation of stress. The growth of SKOV-3 xenografts in the stress group showed a more rapid trend than that in the control. The mean weight of tumors that were removed at the end of the experiment increased by 71.7% in the stress group as compared to the control. In order to explore the underlying mechanisms, we first determined the serum levels of norepinephrine (NE) and interleukin 10 (IL-10) in the mice using an enzyme-linked immunoabsorbent assay (ELISA) and then analyzed protein expression profiles of SKOV-3 xenografts using a proteomics-based approach combining two-dimensional electrophoresis with ultra performance liquid chromatography-electrospray tandem mass spectrometry (nanoUPLC-ESI-MS/MS). Results demonstrated that serum levels of NE and IL-10 were obviously increased in the mice receiving 6 h of immobilization daily for 42 days. In xenografts exposed to stress, a tumor promoting protein nm23 was significantly upregulated while a tumor suppressing protein NDRG1 was obviously downregulated, which were confirmed by subsequent Western blot analysis. Results obtained in the current study suggested that chronic stress promoted the growth of ovarian carcinoma in nude mice through increasing serum levels of NE and IL-10 and altering nm23 and NDRG1 expression in tumor tissues.