Hang Qun, Sun Ruochuan, Jiang Congqiao, Li Yongxiang
aDepartment of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei bDepartment of Gastric and Intestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Anticancer Drugs. 2015 Jul;26(6):632-40. doi: 10.1097/CAD.0000000000000227.
Gastric cancer is now the fourth most common malignancy and the second leading cause of death because of cancer. The resistance to anticancer drugs is the main cause of chemotherapy failure. In this study, we explored the role of Notch 1 and long noncoding RNA (lncRNA) in drug-resistant gastric cancer formation. First, we found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer cell lines SGC7901/DDP and BGC823/DDP cells. Then, we constructed a Notch 1 overexpression vector plasmid; after successful transfection, the SGC7901 and BGC823 cells highly expressed Notch 1. Moreover, the expression of multidrug resistance-associated protein 1 (MRP1), P-glycoprotein, increased significantly and the apoptosis of SGC7901 and BGC823 cells obviously reduced. We further screened out the lncRNA AK022798 involved in this process. Furthermore, we used siRNA to interfere with lncRNA AK022798 expression, and found that the expression of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8 obviously increased. These results suggest that Notch 1 can promote the lncRNA AK022798 expression and result in the formation of SGC7901/DDP and BGC823/DDP cells. It may provide a new, useful method for gastric cancer chemotherapy.
胃癌目前是第四大常见恶性肿瘤，也是癌症死亡的第二大主要原因。对抗癌药物的耐药性是化疗失败的主要原因。在本研究中，我们探讨了Notch 1和长链非编码RNA（lncRNA）在耐药性胃癌形成中的作用。首先，我们发现Notch 1在顺铂耐药的胃癌细胞系SGC7901/DDP和BGC823/DDP细胞中高表达。然后，我们构建了Notch 1过表达载体质粒；成功转染后，SGC7901和BGC823细胞中Notch 1高表达。此外，多药耐药相关蛋白1（MRP1）、P-糖蛋白的表达显著增加，SGC7901和BGC823细胞的凋亡明显减少。我们进一步筛选出参与此过程的lncRNA AK022798。此外，我们使用小干扰RNA（siRNA）干扰lncRNA AK022798的表达，发现SGC7901/DDP和BGC823/DDP细胞中MRP1和P-糖蛋白的表达显著降低，它们的凋亡以及半胱天冬酶3和半胱天冬酶8的表达明显增加。这些结果表明，Notch 1可促进lncRNA AK022798的表达并导致SGC7901/DDP和BGC823/DDP细胞的形成。这可能为胃癌化疗提供一种新的有用方法。
