Wang Yafang, Liu Lili, Liu Xiangqiang, Zhang Hui, Liu Jiaming, Feng Bin, Shang Yulong, Zhou Lin, Wu Kaichun, Nie Yongzhan, Zhang Hongbo, Fan Daiming
State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
Tumour Biol. 2013 Aug;34(4):2205-14. doi: 10.1007/s13277-013-0758-3. Epub 2013 Apr 6.
Multidrug resistance (MDR) is a major clinical obstacle in treatment of gastric cancer (GC) and it accounts for the majority of cancer-related mortalities. Shugoshin1 (SGO1) is an important player in appropriate chromosome segregation and is involved in tumorigenesis. In this study, we found endogenous SGO1 overexpression in the multidrug-resistant GC cell lines SGC7901/VCR and SGC7901/ADR compared with their parental cell line SGC7901. By enhancing expression of SGO1, sensitivity of SGC7901 cells to vincristine (VCR), adriamycin, 5-fluorouracil (5-FU), and cisplatin (CDDP) was significantly diminished. Silencing its expression resulted in enhanced sensitivity of SGC7901/VCR and SGC7901/ADR cells to these antitumor drugs. Additionally, we confirmed that SGO1 increased capacity of cells to enable adriamycin (ADR) efflux and inhibit drug-induced apoptosis by regulating MRP 1, Bcl-2, and Bax genes so as to confer a MDR phenotype to GC cells. In brief, these findings suggest that SGO1 promotes MDR of GC cells and may be useful as a novel therapeutic target for preventing or reversing MDR.
多药耐药（MDR）是胃癌（GC）治疗中的主要临床障碍，也是癌症相关死亡的主要原因。Shugoshin1（SGO1）在适当的染色体分离中起重要作用，并参与肿瘤发生。在本研究中，我们发现与亲代细胞系SGC7901相比，多药耐药的GC细胞系SGC7901/VCR和SGC7901/ADR中内源性SGO1过表达。通过增强SGO1的表达，SGC7901细胞对长春新碱（VCR）、阿霉素、5-氟尿嘧啶（5-FU）和顺铂（CDDP）的敏感性显著降低。沉默其表达导致SGC7901/VCR和SGC7901/ADR细胞对这些抗肿瘤药物的敏感性增强。此外，我们证实SGO1通过调节MRP 1、Bcl-2和Bax基因增加细胞使阿霉素（ADR）外排的能力并抑制药物诱导的凋亡，从而赋予GC细胞MDR表型。简而言之，这些发现表明SGO1促进GC细胞的MDR，可能作为预防或逆转MDR的新治疗靶点。
