Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Evid Based Complement Alternat Med. 2013;2013:265061. doi: 10.1155/2013/265061. Epub 2013 May 25.
Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Thus, there is a great need to develop new treatment regimens to suppress tumor cells that have escaped surgical removal or that may have already disseminated. We have found that tetrandrine (TET) exhibits anticolon cancer activity. Here, we investigate the inhibition effect of TET to breast cancer metastasis, angiogenesis and its molecular basis underlying TET's anticancer activity. We compare TET with chemotherapy drug doxorubicin in 4T1 tumor bearing BALB/c mice model and find that TET exhibits an anticancer metastatic and antiangiogenic activities better than those of doxorubicin. The lung metastatic sites were decreased by TET, which is confirmed by bioluminescence imaging in vivo. On the other hand, laser doppler perfusion imaging (LDI) was used for measuring the blood flow of tumor in 4T1-tumor bearing mice. As a result, the local blood perfusion of tumor was markedly decreased by TET after 3 weeks. Mechanistically, TET treatment leads to a decrease in p-ERK level and an increase in NF- κ B levels in HUVECs. TET also regulated metastatic and angiogenic related proteins, including vascular endothelial growth factor, hypoxia-inducible factor-1 α , integrin β 5, endothelial cell specific molecule-1, and intercellular adhesion molecule-1 in vivo.
转移仍然是癌症最致命的方面，仍然难以直接治疗。因此，非常需要开发新的治疗方案来抑制已经逃脱手术切除或可能已经扩散的肿瘤细胞。我们发现汉防己甲素（TET）具有抗结肠癌活性。在这里，我们研究了 TET 对乳腺癌转移、血管生成的抑制作用及其抑制癌症活性的分子基础。我们将 TET 与化疗药物阿霉素在 4T1 荷瘤 BALB/c 小鼠模型中进行比较，发现 TET 比阿霉素具有更好的抗癌转移和抗血管生成活性。TET 减少了肺转移部位，这通过体内生物发光成像得到了证实。另一方面，激光多普勒灌注成像（LDI）用于测量 4T1 荷瘤小鼠肿瘤的血流。结果表明，TET 治疗后 3 周肿瘤的局部血流明显减少。在机制上，TET 处理导致 HUVECs 中 p-ERK 水平降低和 NF-κB 水平升高。TET 还调节了转移性和血管生成相关蛋白，包括血管内皮生长因子、缺氧诱导因子-1α、整合素β5、内皮细胞特异性分子-1 和细胞间黏附分子-1。
