Department of Thoracic and Cardiovascular Surgery, No. 4 People's Hospital of Wuxi City, Wuxi City, PR China.
Oncol Res. 2013;20(9):411-7. doi: 10.3727/096504013X13657689383094.
Survivin is overexpressed in most of human cancer cells and tissues. Its overexpression is associated with apoptosis inhibition, drug resistance, and poor prognosis. In this study, we investigated the effect of adeno-associated virus (AAV)-mediated survivin mutant Cys84Ala [rAAV-Sur-Mut(C84A)] on gastric cancer growth. Sur-Mut(C84A) was subcloned into the AAV expression vector pAM/CAG to generate recombinant (r)AAV-Sur-Mut(C84A) virus. Cell survival was determined by the MTT method. Apoptosis was measured by FACS analysis and TUNEL. Tumor growth was assessed using a xenograft mouse model. Results showed that treatment of rAAV-Sur-Mut(C84A) virus significantly reduced cell survival, induced apoptosis, and sensitized gastric cancer cells to 5-fluorouracil in vitro. Furthermore, treatment of rAAV-Sur-Mut(C84A) virus markedly induced apoptosis and inhibited gastric cancer growth in vivo. Moreover, rAAV-Sur-Mut(C84A) treatment strongly enhanced the antitumor activity of 5-fluorouracil. Our results suggest that the combination of rAAV-Sur-Mut(C84A) with chemotherapy may be a promising strategy for gastric cancer therapy.
Survivin 在大多数人类癌细胞和组织中过度表达。其过度表达与细胞凋亡抑制、耐药和预后不良有关。在这项研究中，我们研究了腺相关病毒 (AAV) 介导的 survivin 突变型 Cys84Ala [rAAV-Sur-Mut(C84A)] 对胃癌生长的影响。Sur-Mut(C84A) 被亚克隆到 AAV 表达载体 pAM/CAG 中，以生成重组 (r)AAV-Sur-Mut(C84A) 病毒。通过 MTT 法测定细胞存活率。通过 FACS 分析和 TUNEL 测定凋亡。使用异种移植小鼠模型评估肿瘤生长。结果表明，rAAV-Sur-Mut(C84A) 病毒处理显著降低细胞存活率，诱导细胞凋亡，并增强胃癌细胞对体外 5-氟尿嘧啶的敏感性。此外，rAAV-Sur-Mut(C84A) 病毒处理显著诱导体内细胞凋亡并抑制胃癌生长。此外，rAAV-Sur-Mut(C84A) 处理强烈增强了 5-氟尿嘧啶的抗肿瘤活性。我们的结果表明，rAAV-Sur-Mut(C84A) 与化疗的联合可能是胃癌治疗的一种有前途的策略。
