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

Abstract

Arsenic trioxide (As 2O 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 2O 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 2O 3, the ratio of living cells to dead cells decreased significantly, and the IC 50 value was 5.23 μmol/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 24 h, and the cells showed apoptosis in a time-dependent manner; As 2O 3 can inhibit the activity of telomerase of the cell extraction, obviously, in a concentration-dependent and time-dependent manner after 24 h. As to the inhibition impact of As 2O 3 on the xenograft model of nude mice in the two indexes, tumor volume and weight, there was a significant difference between As 2O 3 and the control group; there was no difference between As 2O 3 and the fluorouracil (5-FU) group; in the group of peritoneal injections of As 2O 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 2O 3 inhibited LS-174T cell growth mainly by inducing cell apoptosis, partly by the inhibition of telomerase activity.