In the current study, we examined whether the combination of tumor vasculature-targeted gene therapy with adeno-associated virus bacteriophage-tumor necrosis factor-α (AAVP-TNF-α) and/or the orally administered LCL161, an antagonist of inhibitors of apoptosis proteins (IAPs), enhanced antitumor efficacy without systemic toxicity. M21 human melanoma xenografts were grown subcutaneously in nude mice. Mice were treated according to one of four treatment regimens: AAVP-TNF-α alone (AAVP-TNF-α plus sodium acetate-acetic acid (NaAc) buffer) via tail vein injection; LCL161 alone (phosphate-buffered saline (PBS) plus LCL161) via oral gavage; AAVP-TNF-α plus LCL161; and PBS plus NaAc Buffer as a control group. Tumor volume, survival and toxicity were analyzed. AAVP trafficking and TNF-α production in vivo were detected on days 7 and 21 by real-time PCR, enzyme-linked immunosorbent assay and immunofluorescence. The levels of apoptosis and activation of caspases were assessed on days 7 and 21 by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling) and immunofluorescence assays. Our results showed that the combination of AAVP-TNF-α and LCL161 significantly inhibited tumor growth and prolonged survival in mice with melanoma xenografts. The combination of AAVP-TNF-α and LCL161 was also significantly more effective than either agent alone, showing a synergistic effect without systemic toxicity.

译文

在本研究中,我们检查了肿瘤脉管系统靶向基因治疗与腺相关病毒噬菌体肿瘤坏死因子-α (AAVP-TNF-α) 和/或口服LCL161 (凋亡蛋白抑制剂的拮抗剂) 的组合,增强抗肿瘤疗效,无全身毒性。M21人黑素瘤异种移植物在裸鼠皮下生长。根据四种治疗方案之一对小鼠进行治疗: 尾静脉注射单独使用AAVP-TNF-α (AAVP-TNF-α 加乙酸钠-乙酸 (NaAc) 缓冲液); 单独使用LCL161 (磷酸盐缓冲盐水 (PBS) 加LCL161) 通过口服灌胃; AAVP-TNF-α 加LCL161; PBS加NaAc缓冲液作为对照组。分析肿瘤体积、存活率和毒性。通过实时PCR,酶联免疫吸附测定和免疫荧光在第7天和第21天检测了体内AAVP的运输和TNF-α 的产生。通过TUNEL (末端脱氧核苷酸转移酶介导的dUTP缺口末端标记) 和免疫荧光测定,在第7天和第21天评估了胱天蛋白酶的凋亡和活化水平。我们的结果表明,AAVP-TNF-α 和LCL161的组合显着抑制了黑色素瘤异种移植物小鼠的肿瘤生长并延长了生存期。AAVP-TNF-α 和LCL161的组合也比单独使用任何一种药物有效,显示出协同作用而没有全身毒性。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录