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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)1 ml加As2O3 2 mg(实验组)和UFLP 1 ml(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-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 correlation between As2O3 in inducing apoptosis of malignant tumor cells and survivin in hepatic artery chemoembolization (TACE). Methods Sixteen Japanese white rabbits with VX2 tumor model were transplanted into the left and right lobe of the liver. The rabbits were randomly divided into 2 groups. The transplanted tumor was treated with transluminal hepatic artery (UFLP) Add As2O3 2 mg (experimental group) and UFLP 1 ml (control group). After 3 weeks of administration, all the animals were sacrificed and the tumor tissues, peritumoral tissues and normal liver tissues were harvested for terminal deoxynucleotidyl transferase-biotin dUTP nick end labeling (TUNEL) staining to observe apoptotic tumor cells, and immunized Survivin protein expression was detected by histochemical staining. Results A large number of apoptotic cells were observed in the experimental group and no apoptotic cells were observed in the paracancerous tissues and normal tissues. The control group showed no yellow particles in the tumor tissues, paracancerous tissues and normal tissues Dead cells. Survivin protein expression was 100% (16/16) in the control group, of which 12 were strongly positive and 4 were weakly positive, while the expression of survivin protein was 0 in the paracancer and normal tissues. The expression of survivin protein in the experimental group was 37.5% (6/16), of which 2 were strongly positive and 4 were weakly positive. The expression rates of survivin protein in the adjacent and normal tissues were also 0. The difference of survivin protein expression in the two tumor tissues was statistically significant (P <0.05). At the same time, there was significant difference of survivin protein expression between adjacent cancer tissues and adjacent normal tissues (P <0.01). Conclusion As2O3 can promote tumor cell apoptosis by inhibiting the expression of survivin protein in tumor cells.