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BRM270通过下调音猬因子信号通路抑制CD44阳性胰腺导管腺癌细胞的增殖。

BRM270 Inhibits the Proliferation of CD44 Positive Pancreatic Ductal Adenocarcinoma Cells via Downregulation of Sonic Hedgehog Signaling.

作者信息

Huynh Do Luong, Koh Hyebin, Chandimali Nisansala, Zhang Jiao Jiao, Kim Nameun, Kang Tae Yoon, Ghosh Mrinmoy, Gera Meeta, Park Yang-Ho, Kwon Taeho, Jeong Dong Kee

机构信息

Laboratory of Animal Genetic Engineering and Stem Cell Biology, Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Republic of Korea.

Chongqing Key Laboratory of Forage and Herbivore, College of Animal Science and Technology, Southwest University, Chongqing 400715, China.

出版信息

Evid Based Complement Alternat Med. 2019 Feb 24;2019:8620469. doi: 10.1155/2019/8620469. eCollection 2019.

Abstract

Pancreatic cancer has a poor survival rate as compared to other types of cancer. Surface marker CD44 plays important role in epithelial-mesenchymal transition and cancer stem cell phenotype. Therefore, targeting CD44 positive pancreatic cancer cells might enhance therapies effectiveness. Our previous studies indicated the antitumorigenesis effect of BRM270 in osteosarcoma, lung cancer, and glioblastoma; however there is no evidence on BRM270 impacts on pancreatic cancer growth. In this study, we investigated the effect of BRM270 on the isolated CD44 positive pancreatic ductal adenocarcinoma cells (CD44 PDAC). Results showed that CD44 positive cells undergo apoptosis induced by BRM270. Moreover, BRM270 also inhibits stemness and metastasis traits in CD44 PDAC via Sonic hedgehog signaling pathway and SALL4 expression. study indicated that tumor growth derived from CD44 PDAC was suppressed as daily uptake by BRM270 5 mg/kg. These data suggest the alternative approach in antipancreatic tumorigenesis via herbal plants extract and selectively targeting CD44 PDAC cells in tumor.

摘要

与其他类型的癌症相比,胰腺癌的生存率很低。表面标志物CD44在上皮-间质转化和癌症干细胞表型中起着重要作用。因此,靶向CD44阳性胰腺癌细胞可能会提高治疗效果。我们之前的研究表明BRM270在骨肉瘤、肺癌和胶质母细胞瘤中具有抗肿瘤发生作用;然而,尚无证据表明BRM270对胰腺癌生长有影响。在本研究中,我们研究了BRM270对分离出的CD44阳性胰腺导管腺癌细胞(CD44 PDAC)的作用。结果显示,CD44阳性细胞会发生由BRM270诱导的凋亡。此外,BRM270还通过音猬因子信号通路和SALL4表达抑制CD44 PDAC中的干性和转移特性。研究表明,当每天以5 mg/kg的剂量摄取BRM270时,源自CD44 PDAC的肿瘤生长受到抑制。这些数据表明,通过植物提取物和选择性靶向肿瘤中的CD44 PDAC细胞,在抗胰腺癌发生方面有另一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a2a/6462339/1be820566f0f/ECAM2019-8620469.001.jpg

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