Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition.
Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition.
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DOI：
10.1371/journal.pone.0040480
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hu X
中科院分区：
文献类型：
--
作者：
Liu Z;Zhang B;Liu K;Ding Z;Hu X
转移是癌症相关死亡的主要原因，靶向转移过程已被提出作为对抗癌症的策略。因此，开发靶向转移过程的候选药物是非常重要的。在前期研究中，我们发现五味子素B（SchB）是一种天然存在的二苯并环辛二烯木脂素，具有很低的毒性，可以抑制肿瘤的转移。BALB/c小鼠皮下接种或通过尾静脉注射鼠乳腺癌4 T1细胞。将小鼠分为Sch B处理组和对照组。观察原发肿瘤生长、局部浸润、肺和骨转移及生存时间。肿瘤活检进行了免疫和组织病理学检查。检测Sch B对TGF-β诱导的4 T1和原代人乳腺癌细胞上皮间质转化（EMT）的抑制作用。Sch B能显著抑制4 T1细胞的自发性肺转移和骨转移。对原发性肿瘤生长没有显著影响，并显著延长了这些小鼠的存活时间。Sch B不能抑制经尾静脉注射的4 T1细胞的肺转移。在预先存在肿瘤的小鼠中，延迟开始使用Sch B治疗并没有减少肺转移。提示Sch B参与了局部侵袭。组织学证据表明，Sch B组的原发肿瘤局部浸润性明显低于对照组。体外实验表明，Sch B能抑制TGF-β诱导的4 T1细胞和原代人乳腺癌细胞的EMT。Sch B通过抑制EMT而显著抑制4 T1细胞的肺和骨转移，提示其在靶向肿瘤转移过程中具有潜在的应用价值。
Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposed as a strategy to combat cancer. Therefore, to develop candidate drugs that target the process of metastasis is very important. In the preliminary studies, we found that schisandrin B (Sch B), a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could suppress cancer metastasis. BALB/c mice were inoculated subcutaneously or injected via tail vein with murine breast cancer 4T1 cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-β induced epithelial-mesenchymal transition (EMT) of 4T1 and primary human breast cancer cells was assayed. Sch B significantly suppressed the spontaneous lung and bone metastasis of 4T1 cells inoculated s.c. without significant effect on primary tumor growth and significantly extended the survival time of these mice. Sch B did not inhibit lung metastasis of 4T1 cells that were injected via tail vein. Delayed start of treatment with Sch B in mice with pre-existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. Histopathological evidences demonstrated that the primary tumors in Sch B group were significantly less locally invasive than control tumors. In vitro assays demonstrated that Sch B could inhibit TGF-β induced EMT of 4T1 cells and of primary human breast cancer cells. Sch B significantly suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT, suggesting its potential application in targeting the process of cancer metastasis.
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影响因子：
4.7
作者：
Lee YH;Albig AR;Regner M;Schiemann BJ;Schiemann WP
通讯作者：
Schiemann WP
影响因子：
46.9
作者：
Ma L;Reinhardt F;Pan E;Soutschek J;Bhat B;Marcusson EG;Teruya-Feldstein J;Bell GW;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
3.7
作者：
Bandyopadhyay A;Wang L;Agyin J;Tang Y;Lin S;Yeh IT;De K;Sun LZ
通讯作者：
Sun LZ
影响因子：
11.2
作者：
Medina-Ramirez CM;Goswami S;Smirnova T;Bamira D;Benson B;Ferrick N;Segall J;Pollard JW;Kitsis RN
通讯作者：
Kitsis RN
影响因子：
13.5
作者：
Ding, Wei;You, Hanning;Dang, Hien;LeBlanc, Francis;Galicia, Vivian;Lu, Shelly C.;Stiles, Bangyan;Rountree, C. Bart
通讯作者：
Rountree, C. Bart