State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Cancer Gene Ther. 2012 Feb;19(2):101-9. doi: 10.1038/cgt.2011.71. Epub 2011 Nov 4.
Vesicular stomatitis virus (VSV) matrix protein (MP) can induce in vitro apoptosis of tumor cells in the absence of other viral components. Here, the antitumor activity of VSV-MP against lung adenocarcinoma was investigated in vivo. A pVAX-plasmid DNA encoding VSV-MP and control empty vectors (pVAX) were constructed and wrapped-up with liposome. A549 and Spc-A1 human lung adenocarcinoma cells were transfected with liposomal-VSV-MP (Lip-MP) or Lip-pVAX and then examined for cell viability or apoptosis using Hoechst/propidium iodide staining by flow cytometry, and further demonstrated by caspase/poly ADP-ribose polymerase (PARP) cleavage analysis. For the in vivo study, A549 and Spc-A1 lung carcinoma models in nude mice were established and randomly assigned into three groups to receive eight 2-weekly intravenous administrations of medium alone as control, Lip-pVAX or Lip-MP, respectively. Subsequently, Lip-MP significantly reduced tumor growth and prolonged the survival of tumor-bearing mice compared with Lip-pVAX and control agents (P<0.05), with much higher apoptosis index of both in vivo and in vitro tumor cells, respectively (P<0.05). In addition, in vivo antitumoral effect was associated with natural killer-(NK) cell congregation without evidence of toxicity. These observations suggest that systemically delivering Lip-MP has a specific dual antitumor activity in human lung adenocarcinoma by inducing apoptosis and possibly stimulating NK-cell responses, it may provide a clue for developing new therapeutic approaches against human lung adenocarcinoma.
水疱性口炎病毒（VSV）基质蛋白（MP）可在缺乏其他病毒成分的情况下诱导肿瘤细胞体外凋亡。本研究旨在体内研究 VSV-MP 对肺腺癌的抗肿瘤活性。构建了一种 pVAX 质粒 DNA，可编码 VSV-MP 和对照空载体（pVAX），并用脂质体包裹。A549 和 Spc-A1 人肺腺癌细胞用脂质体-VSV-MP（Lip-MP）或 Lip-pVAX 转染，然后通过流式细胞术用 Hoechst/碘化丙啶染色检测细胞活力或凋亡，并通过 caspase/多聚 ADP-核糖聚合酶（PARP）切割分析进一步证实。在体内研究中，建立了裸鼠 A549 和 Spc-A1 肺腺癌模型，并随机分为三组，分别接受 8 次为期 2 周的静脉注射，对照组为中介质，Lip-pVAX 或 Lip-MP。随后，与 Lip-pVAX 和对照剂相比，Lip-MP 显著降低了肿瘤生长并延长了荷瘤小鼠的存活时间（P<0.05），体内和体外肿瘤细胞的凋亡指数均明显升高（P<0.05）。此外，体内抗肿瘤作用与自然杀伤（NK）细胞聚集有关，无毒性证据。这些观察结果表明，通过诱导细胞凋亡和可能刺激 NK 细胞反应，系统给予 Lip-MP 对人肺腺癌具有特异性的双重抗肿瘤活性，为开发针对人肺腺癌的新治疗方法提供了线索。
