Department of Otolaryngology Head and Neck Surgery, the Second Hospital of Tianjin Medical University, Tianjin, China.
Anat Rec (Hoboken). 2014 Feb;297(2):215-21. doi: 10.1002/ar.22832. Epub 2013 Dec 24.
Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx, and chemoresistance is an essential aspect of NPC chemotherapy failure. Sorcin has been implicated in multidrug resistance (MDR) of many types of human tumor. However, the effect and mechanism of Sorcin in MDR of human NPC is not fully clear. In this report, we silenced Sorcin in human NPC CNE2/DDP cells, and explored the role of Sorcin in MDR reversal. The results showed an increased cytotoxicity of cisplatin and intracellular accumulation of Rhodamine-123 and glutathione depletion in Sorcin silencing CNE2/DDP cells. We also found a decreased messenger RNA and protein expression of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase-π (GST-n), RhoE, Bcl-2, and Survivin in Sorcin silencing CNE2/DDP cells. The increased expression of PTEN and decreased expression of p-Akt and NF-κB suggested that the key cellular signaling pathways were triggered by Sorcin silencing. We concluded that Sorcin silencing would contribute to establish a potent target point for MDR reversal.
鼻咽癌（NPC）是最常见的原发于鼻咽部的癌症之一，而化疗耐药是 NPC 化疗失败的重要方面。Sorcin 与多种人类肿瘤的多药耐药（MDR）有关。然而，Sorcin 在人 NPC 的 MDR 中的作用和机制尚不完全清楚。在本报告中，我们在人 NPC CNE2/DDP 细胞中沉默了 Sorcin，并探讨了 Sorcin 在 MDR 逆转中的作用。结果表明，沉默 Sorcin 可增加顺铂的细胞毒性、增加 Rhodamine-123 的细胞内蓄积和谷胱甘肽耗竭。我们还发现，沉默 Sorcin 的 CNE2/DDP 细胞中多药耐药基因（MDR1）、多药耐药相关蛋白 1（MRP1）、切除修复交叉互补基因 1（ERCC1）、谷胱甘肽 S-转移酶-π（GST-n）、RhoE、Bcl-2 和 Survivin 的信使 RNA 和蛋白表达降低。PTEN 表达增加，p-Akt 和 NF-κB 表达降低，提示 Sorcin 沉默触发了关键的细胞信号通路。我们的结论是，沉默 Sorcin 将有助于建立一个有效的 MDR 逆转靶点。
