CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2
CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2
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DOI：
10.1007/s10495-013-0831-9
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发表时间：
2013-07-01
期刊：
影响因子：
7.2
通讯作者：
Ouyang, Xuenong
中科院分区：
文献类型：
--
作者：
Chen, Xiong;Zheng, Peichan;Ouyang, Xuenong
我们之前的报告表明钙周期蛋白结合蛋白或 Siah-1 相互作用蛋白 (CacyBP/SIP) 在 SGC7901/ADR 细胞系中过度表达。然而，CacyBP/SIP 在胰腺癌多药耐药（MDR）发展中的潜在作用仍不确定。在本文中，我们研究了CacyBP/SIP在胰腺癌细胞MDR中的作用及其可能的机制，发现与亲代细胞PC-3相比，CacyBP/SIP在吉西他滨诱导的MDR胰腺癌细胞PC-3/Gem中过表达。 CacyBP/SIP表达上调可增强PC-3细胞对化疗药物的耐药性，抑制阿霉素诱导的细胞凋亡，同时减少细胞内阿霉素的积累。此外，CacyBP/SIP 可以显着上调 P-gp、Bcl-2 的表达和 MDR1 基因的转录。此外，使用RNA干扰或P-gp抑制剂降低CacyBP/SIP表达可以部分逆转CacyBP/SIP介导的MDR。简而言之，我们的研究表明，CacyBP/SIP可以通过增加P-gp和Bcl-2的表达来增强胰腺癌细胞的MDR表型，从而抑制胰腺癌细胞的凋亡。
Our former report indicates that calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) is over-expressed in the SGC7901/ADR cell line. However, the potential role of CacyBP/SIP in the development of multidrug resistance (MDR) of pancreatic cancer is still uncertain. In this paper, we investigated the role of CacyBP/SIP in MDR of pancreatic cancer cells and its possible underlying mechanisms, and found that CacyBP/SIP was over-expressed in the Gemcitabine induced MDR pancreatic cancer cell PC-3/Gem compared with its parental cell PC-3. Up-regulation of CacyBP/SIP expression could enhance resistance of chemotherapy drugs on PC-3 cells and inhibit Adriamycin-induced apoptosis accompanied by decreased accumulation of intracellular Adriamycin. Furthermore, CacyBP/SIP could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene. In addition, the decrease of CacyBP/SIP expression using RNA interference or P-gp inhibitor could partially reverse CacyBP/SIP-mediated MDR. In brief, our study demonstrated that CacyBP/SIP could enhance the MDR phenotype of pancreatic cancer cells by increasing the expression of P-gp and Bcl-2, thus inhibiting apoptosis of pancreatic cancer cell.