新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 癌症研究 » Mol Carcinogen:达沙替尼有望用于治疗乳腺癌和其他癌症

Mol Carcinogen:达沙替尼有望用于治疗乳腺癌和其他癌症

来源:生物谷 2014-08-21 09:27

2014年8月21日讯 /生物谷BIOON/--据Loyola大学芝加哥Stritch医学院研究人员证实:白血病药物—达沙替尼,很有希望用于治疗皮肤癌,乳腺癌和其他一些癌症。
 
达沙替尼属多酪氨酸激酶抑制剂,用于治疗白血病。但用达沙替尼其他类型肿瘤细胞时,研究人员发现该药物能使肿瘤细胞聚集在一起,从而防止它们迁移。没有迁移能力,癌细胞不能转移。

Mitchell Denning博士和他的同事发现了达沙替尼抑制肿瘤细胞间黏附的背后分子机制。研究人员在Molecular Carcinogenesis杂志报告了他们的研究结果。

达沙替尼(商品名Sprycel)已被批准用于治疗某些类型的白血病。它针对的是一种叫做BCR-ABL的蛋白,后者促进癌细胞的生长。

BCR-ABL类似于Fyn蛋白质,后者在其他恶性肿瘤包括乳腺癌,脑癌,皮肤癌和头颈部癌症中发现。Fyn与细胞-细胞粘连和细胞迁移相关联。

Denning及其同事发现,在实验室中用达沙替尼处理肿瘤细胞,造成肿瘤细胞聚集在一起,阻止了细胞的迁移。他们在乳腺癌细胞中发现类似的结果。虽然达沙替尼并没有消除Fyn,但它确实抑制蛋白质活性。

研究人员还发现,达沙替尼能减少皮肤癌小鼠的肿瘤数量和大小。Denning指出,临床试验正在进行中,以测试达沙替尼对黑色素瘤,前列腺癌,胰腺癌,子宫内膜癌,胃肠道间质癌,卵巢癌,多发性骨髓瘤,霍奇金淋巴瘤和急性淋巴细胞性白血病的治疗作用。

​Denning认为,这项研究提示达沙替尼可以应用于许多不同类型癌症的治疗。(生物谷Bioon.com)

Targeting Fyn in Ras-transformed cells induces F-actin to promote adherens junction-mediated cell–cell adhesion

Sarah E. Fenton, Kelli A. Hutchens andMitchell F. Denning

Fyn, a member of the Src family kinases (SFK), is an oncogene in murine epidermis and is associated with cell–cell adhesion turnover and induction of cell migration. Additionally, Fyn upregulation has been reported in multiple tumor types, including cutaneous squamous cell carcinoma (cSCC). Introduction of active H-Ras(G12V) into the HaCaT human keratinocyte cell line resulted in upregulation of Fyn mRNA (200-fold) and protein, while expression of other SFKs remained unaltered. Transduction of active Ras or Fyn was sufficient to induce an epithelial-to-mesenchymal transition in HaCaT cells. Inhibition of Fyn activity, using siRNA or the clinical SFK inhibitor Dasatinib, increased cell–cell adhesion and rapidly (5–60?min) increased levels of cortical F-actin. Fyn inhibition with siRNA or Dasatinib also induced F-actin in MDA-MB-231 breast cancer cells, which have elevated Fyn. F-actin co-localized with adherens junction proteins, and Dasatinib-induced cell–cell adhesion could be blocked by Cytochalasin D, indicating that F-actin polymerization was a key initiator of cell–cell adhesion through the adherens junction. Conversely, inhibiting cell–cell adhesion with low Ca2+ media did not block Dasatinib-induced F-actin polymerization. Inhibition of the Rho effector kinase ROCK blocked Dasatinib-induced F-actin and cell–cell adhesion, implicating relief of Rho GTPase inhibition as a mechanism of Dasatinib-induced cell–cell adhesion. Finally, topical Dasatinib treatment significantly reduced total tumor burden in the SKH1 mouse model of UV-induced skin carcinogenesis. Together these results identify the promotion of actin-based cell–cell adhesion as a newly described mechanism of action for Dasatinib and suggest that Fyn inhibition may be an effective therapeutic approach in treating cSCC.

 

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库