Gu Wei, Han Ke-qi, Su Yong-hua, Huang Xue-qiang, Ling Chang-quan
Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Zhong Xi Yi Jie He Xue Bao. 2007 Mar;5(2):155-9. doi: 10.3736/jcim20070211.
To investigate the anti-tumor effect of bufalin and its regulation on Bcl-2 and Bax proteins in orthotopically transplanted tumor of human hepatocellular carcinoma in nude mice.
Orthotopically transplanted tumor of human hepatocellular carcinoma was established in nude mice. The mice were randomly divided into five groups: high-dose bufalin-treated group (1.5 mg/kg), medium-dose bufalin-treated group (1 mg/kg), low-dose bufalin-treated group (0.5 mg/kg), adriamycin-treated group (8.0 mg/kg), and normal saline-treated group. After 25 days, mice were sacrificed. The tumor volume was measured, and the pathological changes of tumor tissues were detected by HE staining to observe the tumor necrosis degree. Cell morphological changes were also observed by an electron microscopy. Label index of tumor cell apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the expressions of Bcl-2 and Bax proteins were determined by immunohistochemical method.
The tumor volume in the bufalin-treated groups was shrunk significantly compared with that in the normal saline-treated group (P<0.01). The survival time of the bufalin-treated groups was prolonged compared with that of the adriamycin-treated group and the normal saline-treated group P<0.05. Apoptotic characteristics could be seen in tumor tissues of the bufalin-treated groups. The label index of tumor cell apoptosis in the bufalin-treated groups (5.87+/-2.13, 8.86+/-2.96 and 10.60+/-3.42 in low-, medium- and high-dose groups respectively) was higher than that in the adriamycin-treated group (3.28+/-0.98) (P<0.05, P<0.01). The expression of Bax was up-regulated, while no changes were detected as to Bcl-2 protein in tumors of the bufalin-treated groups.
Bufalin has significant anti-tumor effect on the orthotopically transplanted tumor of human hepatocellular carcinoma in nude mice. Its effect might be related to up-regulation of Bax protein and inducement of the tumor cell apoptosis.
探讨蟾毒灵对人肝癌裸鼠原位移植瘤的抗肿瘤作用及其对Bcl-2和Bax蛋白的调控作用。
建立人肝癌裸鼠原位移植瘤模型。将小鼠随机分为五组：高剂量蟾毒灵治疗组（1.5 mg/kg）、中剂量蟾毒灵治疗组（1 mg/kg）、低剂量蟾毒灵治疗组（0.5 mg/kg）、阿霉素治疗组（8.0 mg/kg）和生理盐水治疗组。25天后处死小鼠，测量肿瘤体积，HE染色检测肿瘤组织病理变化以观察肿瘤坏死程度，电镜观察细胞形态变化。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）评估肿瘤细胞凋亡标记指数，免疫组化法检测Bcl-2和Bax蛋白表达。
与生理盐水治疗组相比，蟾毒灵治疗组肿瘤体积明显缩小（P<0.01）。与阿霉素治疗组和生理盐水治疗组相比，蟾毒灵治疗组小鼠生存时间延长（P<0.05）。蟾毒灵治疗组肿瘤组织可见凋亡特征。蟾毒灵治疗组肿瘤细胞凋亡标记指数（低、中、高剂量组分别为5.87±2.13、8.86±2.96和10.60±3.42）高于阿霉素治疗组（3.28±0.98）（P<0.05，P<0.01）。蟾毒灵治疗组肿瘤中Bax表达上调，而Bcl-2蛋白未检测到变化。
蟾毒灵对人肝癌裸鼠原位移植瘤具有显著抗肿瘤作用。其作用可能与上调Bax蛋白及诱导肿瘤细胞凋亡有关。
