The regional distributions and frequencies of argyrophil endocrine cells in gastrointestinal (GI) tract of Balb/c-nu/ nu mouse were studied using Grimelius silver stain after abdominal subcutaneous implantation of COLO205. The experimental animals were divided into two groups, one is non-implanted group (Sham) and the other is COLO205-implanted group. Samples were collected from GI tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 21 days after implantation of COLO205 cells (1x10(6) cell/mouse). In this study, argyrophil cells were detected throughout the entire GI tract with various frequencies regardless of implantation. Most of these argyrophil cells in the mucosa of GI tract were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found occasionally in gastric and/or intestinal gland regions. The regional distributions of argyrophil cells in COLO205 were similar to those of Sham. However, significant decreases of argyrophil cells were detected in COLO205 compared to those of Sham except for the jejunum and ileum. In the jejunum and ileum, argyrophil cells in COLO205 showed similar frequencies compared to those of Sham. In the pylorus, the most dramatically decreasement of argyrophil cells were detected in COLO205 compared to that of Sham. Implantation of COLO205 tumor cell line induced severe quantitative changes of argyrophil cell density, and the abnormality in density of GI endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.
Animals ; Cell Line, Tumor ; Colonic Neoplasms/*ultrastructure ; Enteroendocrine Cells/*ultrastructure ; Female ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Silver Staining

OBJECTIVETo study the impact of arsenic trioxide (As2O3) on human colorectal carcinoma LS-174T cells and their activity of telomerase.

METHODSLS-174T cells and xenograft model of nude mice were treated with As2O3. The inhibitory effect of As2O3 on survival of LS-174T cells was determined by MTT assay. Apoptosis was determined by electron microscopy and fluorescence microscopy. Cell cycle was assessed by flow cytometry. Telomerase activity in LS-174T cells was determined by PCR-ELISA kit.

RESULTSWith the increasing concentration of As2O3, the ratio of living cells to dead cells decreased significantly, and the IC50 value was 5.23 micromol/L. Apoptosis curve appeared after 24 h and cells turned to apoptosis in a time-dependent manner. As2O3 inhibited the telomerase activity in cell extraction, obviously in a concentration-dependent and time-dependent manner. Inhibitiory effect of As2O3 on xenograft model of nude mice was observed by tumor volume and weight measurement, showing a significant difference between As2O3 and control groups (P < 0.05).

CONCLUSIONBoth the experiments in vitro and in vivo showed an inhibitory effect of As2O3 on colonrectal cancer S-174T cell growth, probably by induction of apoptosis and inhibition of telomerase activity.

Animals ; Apoptosis ; drug effects ; Arsenicals ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Colonic Neoplasms ; pathology ; prevention & control ; ultrastructure ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Inhibitory Concentration 50 ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Electron ; Microscopy, Fluorescence ; Oxides ; administration & dosage ; pharmacology ; Polymerase Chain Reaction ; methods ; Random Allocation ; Telomerase ; antagonists & inhibitors ; genetics ; metabolism ; Time Factors ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays