三氧化二砷通过抑制Skp2表达来增加胰腺癌细胞对吉西他滨的化疗敏感性。
Arsenic trioxide inhibits Skp2 expression to increase chemosensitivity to gemcitabine in pancreatic cancer cells.
作者信息
Gao Jiankun, Wang Gu, Wu Jingrong, Zuo Yu, Zhang Jing, Chen Jiaqi
机构信息
Department of Basic Medical Science, Sichuan College of Traditional Chinese Medicine Mianyang 621000, Sichuan, China.
Department of Hepatobiliary Pancreatic Surgery, Jilin Province Cancer Hospital Changchun 130012, Jilin, China.
出版信息
Am J Transl Res. 2019 Feb 15;11(2):991-997. eCollection 2019.
Abstract
The S-phase kinase associated protein 2 (Skp2), a member of the F-box protein family, regulates cell cycle progression and is highly expressed in pancreatic cancer (PC). Recently, we reported that arsenic trioxide (ATO) inhibited cell growth and invasion via downregulation of Skp2 in PC cells. Emerging evidence has revealed that Skp2 plays a crucial role in drug resistance in several kinds of cancers. Here, we determined whether ATO enhanced the sensitivity of PC cell lines to gemcitabine (GEM). We found that the combined treatment of ATO and GEM demonstrated strong antitumor effects in Patu8988 and Panc-1 PC cells. In addition, ATO potentiated the effects of GEM via downregulation of the Skp2 pathway in PC cells. Together, these findings suggested that Skp2 may be a promising therapeutic target to overcome resistance to GEM in PC.
摘要
S期激酶相关蛋白2（Skp2）是F-box蛋白家族的成员之一，可调节细胞周期进程，在胰腺癌（PC）中高表达。最近，我们报道三氧化二砷（ATO）通过下调PC细胞中的Skp2来抑制细胞生长和侵袭。新出现的证据表明，Skp2在几种癌症的耐药性中起关键作用。在此，我们确定ATO是否能增强PC细胞系对吉西他滨（GEM）的敏感性。我们发现，ATO与GEM联合处理对Patu8988和Panc-1 PC细胞具有强大的抗肿瘤作用。此外，ATO通过下调PC细胞中的Skp2途径增强了GEM的作用。总之，这些发现表明Skp2可能是克服PC对GEM耐药性的一个有前景的治疗靶点。
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