Paper Information

Title: 

STUDY OF 5HT RECEPTORS EXPRESSION IN HT29 CELL LINE AND HUMAN COLORECTAL CANCER TISSUES BY IMMUNOHISTOCHEMISTRY AND WESTERN BLOT

Type: POSTER
Author(s): ATAEI R.*,ZARINDAST M.R.,AZHDARI SOHEYLA,REZAYAT M.,SHAHRIARI SH.
 
 *DEPARTMENT OF PHARMACOLOGY, TEHRAN UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

Colorectal cancer is one important cause of cancer-related death in the world. Over the last decade, significant progress has been made in the treatment of this malignancy and new chemotherapeutic agents have been introduced. Overall, survivals with metastatic colorectal cancer with new therapeutics have been increased. Recently, Selective Serotonin Reuptake Inhibitors (SSRIs) has been suggested to be used in prevention of colorectal cancer in high risk people. There are also some reports indicating that SSRIs could decrease the risk of colorectal cancer in human. Fluxetine, a novel SSRIs drug, in dosage (10-100 μM) could reduce the growth of cancer cells in vitro and this effect was attributed to its’ effect in increasing serotonin levels in peripheral nerve endings in gastrointestinal tract.However, other reports controversially suggested that SSRIs induced mammary tumours in animals and some malignancies as bladder, prostate and breast cancer in humans. The mitogenic activity of 5-HT may be in part due to 5HT receptor activation, dependent on stimulation of phospholipase C-β/protein kinase C and activation of MAP Kinase. Although there were some reports about role of serotonin receptors in promoting some kind of cancers but there was not any precise study about role of these receptors in colorectal cancer. In this study we have assayed protein expression of some main 5HT receptors as 5HT1A, 1B, 1D, 5HT2A, 2B, 5HT3 and 5HT4 with Immunhistochemistry and western blotting. Also for study of the effect of these receptors agonists and antagonists on colorectal cancer cell line (HT29 Cell line), we used MTT assay procedure. We assayed apoptotic effect of theses agonists and antagonists on HT29 cell line with TUNEL cytotoxicity in situ test as well. Our results showed that 5HT1B, 5HT2A and 5HT3 receptors had the highest expression in cell line and tissues and 5HT1B selective antagonist had the best antimitogenic and anti apoptotic effect and can be a good candidate for future colorectal chemotherapy researches.

 
Keyword(s): 5HT RECEPTORS, COLORECTAL CANCER, IMMUNOHISTOCHEMISTRY, HT29 CELL LINE
 
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