National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, People's Republic of China.
Oncol Res. 2009;18(1):1-8. doi: 10.3727/096504009789745647.
The studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts to evaluate the chemotherapeutic potential of selenium containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet. We explored the anticancer effect of SSe and SeMet administered by IP injection for 21 days. We observed the pathologic changes and the cell apoptosis in tumor tissue by HE staining and TUNNEL assay after HSSe and SeMet treatment. GSH level and antioxidant enzyme GPX activity in tumor tissues were assessed. In addition, Western blotting was used to detect the expression of apoptosis-related proteins. The results suggested that HSSe and SeMet had significantly inhibited tumor growth in vivo. We also observed the pathologic changes and cell apoptosis in tumor tissues after HSSe and SeMet treatment. GSH level was a bit increased but the GPX activity was reduced. Moreover, SSe and SeMet treatment downregulated the expression of the protein Bcl-xL, increased the expression of Bax, Bad, and Bim, and activated caspase-9. SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer.
这些研究是在荷有人结肠癌细胞系 SW480 异种移植瘤的裸鼠上进行的，旨在评估含硒化合物（如亚硒酸钠[SSe]和硒代蛋氨酸[SeMet]）的化疗潜力。使用了三种抗癌药物剂量，包括每天 0.1 mg/kg 的 SSe（LSSe）、每天 2 mg/kg 的 SSe（HSSe）和每天 2 mg/kg 的 SeMet。我们通过腹腔注射 LSSe 和 SeMet 连续给药 21 天，探讨了它们的抗癌作用。HSSe 和 SeMet 处理后，通过 HE 染色和 TUNNEL 检测观察肿瘤组织的病理变化和细胞凋亡情况。评估了肿瘤组织中的 GSH 水平和抗氧化酶 GPX 活性。此外，还通过 Western blot 检测了凋亡相关蛋白的表达。结果表明，HSSe 和 SeMet 显著抑制了体内肿瘤的生长。我们还观察了 HSSe 和 SeMet 处理后肿瘤组织的病理变化和细胞凋亡情况。GSH 水平略有升高，但 GPX 活性降低。此外，SSe 和 SeMet 处理下调了 Bcl-xL 蛋白的表达，增加了 Bax、Bad 和 Bim 的表达，并激活了 caspase-9。SSe 和 SeMet 可能是选择性、低毒性的抗癌药物，可用于治疗人结肠直肠癌。
