THE MORPHOLOGICAL AND CELLULAR DYNAMIC CHANGES IN ARSENIC TRIOXIDE-TREATED RAT LIVER CANCER / 肿瘤

ABSTRACT

Objective　To study the efficiency of the treatment of experimental hepatocellular carcinoma in rats with arsenic trioxide and to elucidate the possible mechanism.Methods　Wistar rats were fed with diethylnitrosamine (DEN) to induce HCC, then treated with As2O3. The histological changes in liver tissue were observed under microscope, and the cellular dynamic parameters were studied by flow cytometry. Results　Treatment with As2O3 caused HCC cells death via both apoptotic and non-apoptotic mechanisms when the dose was high (5 mg/kg), the necrosis was seldom and apoptosis was common when the dose was appropriate (1 mg/kg). Proliferation index (PI) decreased sharply in high-dose (5 mg/kg) group (P＜0.01), but not in other two (1 mg/kg, 0.2 mg/jg) groups (P＞0.05). However, S phase fraction (SPF) decreased dramatically in all three groups (P＜0.01). Although apoptosis of HCC cells was common in all three groups, it reached the top only when the dose (1 mg/kg) was appropriate (P＜0.001), and it was obviously accompanied with accumulation of cells in G2/M (G2/M restriction). Conclusion　These date demonstrate that arsenic trioxide induces apoptosis of rat HCC cells, and it is closely associated with G2/M restriction when apoptosis reaches the top. The data also suggest that arsenic trioxide can inhibit cell proliferation, which is dose-dependent and time-dependent. The fact that continuous intermittent i.p. injection of arsenic trioxide can also be effective may afford a novel way to use the drug more safely.