临床研究

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

目的探讨As2O3在肝动脉化疗栓塞（TACE）中诱导恶性肿瘤细胞凋亡作用与生存素之间的相关性。方法将肝脏左、右叶分别移植VX2肿瘤模型的16只日本大耳白兔，随机平均分成2组．移植瘤术后3周，经肝动脉插管分别给予超液化碘油（UFLP）1ml加As2O32mg（实验组）和UFLP1ml（对照组）。给药3周后，所有动物均处死，分别取得肿瘤组织、瘤旁组织和正常肝脏组织进行末端脱氧核苷酸转移酶一生物素dUTP切口末端标记法（TUNEL）染色观察凋亡肿瘤细胞，免疫组化染色检测生存素蛋白的表达。结果实验组肿瘤组织中有大量呈黄色的凋亡细胞，癌旁组织及正常组织中未观察到凋亡细胞；对照组肿瘤组织、癌旁组织及正常组织均未发现细胞核内有黄色颗粒的凋亡细胞。对照组肿瘤组织生存素蛋白表达率为100％（16／16），其中强阳性12例，弱阳性4例，癌旁及正常组织中生存素蛋白表达率为0。实验组肿瘤组织生存素蛋白表达为37．5％（6／16），其中强阳性2例，弱阳性4例，癌旁及正常组织中生存素蛋白表达率同样为0。两组肿瘤组织中生存素蛋白表达率差异有统计学意义（P〈0．05）。同时，两组癌组织与癌旁和正常组织中生存素蛋白表达率差异有统计学意义（P〈0．01）。结论As2O3通过抑制肿瘤细胞内生存素蛋白表达促进肿瘤细胞凋亡。

Objective To investigate the relationship between the expression of tumor apoptosis inhibitory protein （survivin） and the apoptosis induced by arsenic trioxide （As2O3） in transeatheter 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 As203 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 As203 can accelerate the apoptosis of the tumor cells by inhibiting the expression of survivin protein.