Effects of cigarette smoking and restraint stress on human colon tumor growth in mice.
BACKGROUND
Cigarette smoking is a risk factor for colon cancer. Studies suggest that stress increases the incidence and promotes the development of cancers. Cigarette smoking and stress are closely associated, as people often smoke under stressful conditions and both of them can activate the adrenergic nervous system.


OBJECTIVE
To investigate the effects of cigarette smoking and restraint stress on colon cancer growth and the possible underlying mechanisms in these pathological processes.


METHODS
Nude mice bearing a HT-29 human colon cancer xenograft were either exposed to cigarette smoke and/or restraint stress. Cotinine and epinephrine levels in plasma of nude mice were measured by enzyme immunoassays. Expression of cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) in tumor tissues were detected by Western blot. Prostaglandin E(2) (PGE(2)) concentrations were determined by enzyme immunoassay.


RESULTS
4% cigarette smoking together with restraint stress 1 h daily for 33 days promoted tumor growth in nude mice. This was accompanied by the increase of plasma levels of cotinine and epinephrine in these animals. They also enhanced the COX-2, Bcl-2 expressions and PGE(2) levels in tumor tissues.


CONCLUSIONS
These findings are important in understanding the pathogenesis of colon cancer, particularly related to cigarette smoking and stress.
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Helen Pui Shan
HP
Wong
Zhi Jie
ZJ
Li
Vivian Yvonne
VY
Shin
Emily Kin Ki
EK
Tai
William Ka Kei
WK
Wu
Le
L
Yu
Chi Hin
CH
Cho
D000230:Adenocarcinoma / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D003110:Colonic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D003367:Cotinine / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005260:Female; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013315:Stress, Psychological / Q000150:complications*; D014183:Transplantation, Heterologous
D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2; D003367:Cotinine; D015232:Dinoprostone; D004837:Epinephrine