ABSTRACT
<p><b>OBJECTIVE</b>To study the impact of arsenic trioxide (As2O3) on human colorectal carcinoma LS-174T cells and their activity of telomerase.</p><p><b>METHODS</b>LS-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.</p><p><b>RESULTS</b>With 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).</p><p><b>CONCLUSION</b>Both 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.</p>
Subject(s)
Animals , Humans , Mice , Apoptosis , Arsenicals , Pharmacology , Cell Cycle , Cell Line, Tumor , Cell Survival , Colonic Neoplasms , Pathology , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Inhibitory Concentration 50 , Mice, Inbred BALB C , Mice, Nude , Microscopy, Electron , Microscopy, Fluorescence , Oxides , Pharmacology , Polymerase Chain Reaction , Methods , Random Allocation , Telomerase , Genetics , Metabolism , Time Factors , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVE</b>To study the effect of tissue environment on the invasiveness of carcinoma cells and the implication of expression of matrix metalloproteinases.</p><p><b>METHODS</b>Tissue from a human gastric carcinoma was transplanted and passaged subcutaneously in nude mice. After the 3rd passage, the xenografts were also transplanted into the abdominal cavity of nude mice. The invasiveness of xenografts at the two locations were observed morphologically and the expressions of MMP-2, MMP-7, MMP-9, MMP-13, TM1-MMP, TM2-MMP and TM3-MMP were monitored by immunohistochemistry.</p><p><b>RESULTS</b>The subcutaneous xenografts of human gastric carcinoma in nude mice presented as expanding outgrowths with limited invasion. Except for MMP-7, the other 6 MMPs (MMP-2, MMP-9, MMP-13, TM1-MMP, TM2-MMP, TM3-MMP) were not expressed in the neoplastic cells nor in the tumor stroma. In contrast, the intra-peritoneal xenografts displayed an invasive growth pattern accompanied by more fibrous stroma. All MMPs examined were expressed in the tumor cells at the invasive fronts and in the adjacent stroma.</p><p><b>CONCLUSIONS</b>Invasiveness and expression of MMPs were obviously diverse in human gastric carcinoma cells when grafted at different anatomic locations in nude mice, thus indicating: (1) There exists a close interaction between tumor cells and surrounding stromal cells. The tissue environment may play a definitive role in the tumor phenotype. (2) The expression of MMPs is closely related to the growth pattern and the invasiveness of tumor cells. MMPs produced by the stroma cells at the invasion front may be linked to the invasiveness of neoplastic cells.</p>