The regulation of As2O3 on the expression of apoptosis inhibitory protein: an experimental study in rabbits with implanted liver tumor

Objective: To investigate the relationship between the expression of tumor apoptosis inhibitory protein (survivin) and the apoptosis induced by arsenic trioxide (As2O3) in transcatheter arterial chemoembolization therapy. Methods: Sixteen Japanese big-ear white rabbits with implanted hepatic VX2 tumor at both right and left hepatic lobes were randomly and equally divided into two groups. Three weeks after the tumor was inoculated, 1 ml lipiodol (UFLP) and 2 mg As2O3 were injected via hepatic arterial cannulation into the rabbits of study group, while only 1 ml UFLP was used for the rabbits in control group. Three weeks later, all the rabbits were sacrificed, and the tumor tissue, the tumor-neighboring tissue and the normal liver were separately collected and sent for TUNEL staining and examinations, which included the observation of apoptosis of tumor cells and the assessment of the expression of survivin protein. Results: In study group, a large number of yellow apoptosis cells was seen in the tumor tissue but no apoptosis cell was found in the tumor-neighboring tissue or in the normal liver tissue. In the control group, no yellow apoptosis cell was observed in the tumor tissue, tumor-neighboring tissue or normal liver tissue. The survivin protein expression rate of the tumor tissue was 100% (16/16) in the control group, including strongly-positive in 12 and weakly-positive in 4 rabbits. In contrast, the survivin protein expression rate of both the tumor- neighboring tissue and the normal tissue was 0%. In study group, the survivin protein expression rate of the tumor tissue was 37.5% (6/16), including strongly-positive in 2 and weakly-positive in 4 cases, and the survivin protein expression rate of both the tumor-neighboring tissue and the normal tissue was 0%. Significant difference in survivin protein expression rate of the tumor tissue existed between two groups (P<0.05). In both groups, the difference in survivin protein expression rate between the tumor tissue and the tumor-neighboring tissue, and between the tumor tissue and the normal tissue was statistically significant (P< 0.01). Conclusion: As2O3 can accelerate the apoptosis of the tumor cells by inhibiting the expression of survivin protein. (authors)