Inhibition on LS-174T cell growth and activity of telomerase in vitro and in vivo by arsenic trioxide.

Arsenic trioxide (As(2)O(3)) shows a significant therapeutic effect upon acute promyelocytic leukemia (APL) and can induce the apoptosis of NB(4) cells, which attracts scholars' great attention. Especially, the therapeutic effect on solid carcinoma has been paid more close attention to. The present study is to evaluate the effect of As(2)O(3) on human colorectal carcinoma cells (LS-174T cell) and the activity of telomerase in vitro and in vivo. This research made use of the electron microscope, polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), fluorescence-activated cell sorter (FACS), MTT in vitro and in vivo (LS-174T xenograft model of nude mice). With the increasing concentration of As(2)O(3), the ratio of living cells to dead cells decreased significantly, and the IC(50) value was 5.23mumol/L; cells of the experimental groups endured a series of morphological changes similar to the features of apoptosis. Apoptosis curve of FACS pictures appeared after 24h, and the cells showed apoptosis in a time-dependent manner; As(2)O(3) can inhibit the activity of telomerase of the cell extraction, obviously, in a concentration-dependent and time-dependent manner after 24h. As to the inhibition impact of As(2)O(3) on the xenograft model of nude mice in the two indexes, tumor volume and weight, there was a significant difference between As(2)O(3) and the control group; there was no difference between As(2)O(3) and the fluorouracil (5-FU) group; in the group of peritoneal injections of As(2)O(3), the cancer cells connected loosely with each other, nucleus changed markedly, and heterochromatin concentrated under the nucleus membrane. From the in vitro and in vivo experiment, we can see that As(2)O(3) inhibited LS-174T cell growth mainly by inducing cell apoptosis, partly by the inhibition of telomerase activity.