Mannan-modified Ad5-PTEN treatment combined with docetaxel improves the therapeutic effect in H22 tumor-bearing mice
Mannan-modified Ad5-PTEN treatment combined with docetaxel improves the therapeutic effect in H22 tumor-bearing mice
复制标题
甘露聚糖修饰的Ad5-PTEN联合多西紫杉醇治疗可提高H22荷瘤小鼠的治疗效果
DOI：
10.2147/ijn.s34022
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发表时间：
2012-01-01
影响因子：
8
通讯作者：
Zhong, Zhirong
中科院分区：
文献类型：
--
作者：
Liu, Zhongbing;Li, Jinwei;Zhong, Zhirong
研究背景抑癌基因PTEN在多种恶性肿瘤中处于失活状态，在细胞凋亡、细胞周期停滞、细胞迁移、细胞扩散等过程中发挥重要作用。对于癌症的基因治疗，最重要的问题之一是基因转染率低。方法为了充分利用腺病毒在基因表达上的优势，我们制备了携带PTEN基因的甘露聚糖修饰重组腺病毒(Man-Ad5-PTEN)，并研究了Man-Ad5-PTEN联合多西紫杉醇(Man-Ad5-PTEN-docetaxel)对小鼠肝癌模型肿瘤生长的影响。结果Man-Ad5-PTEN在体内能有效抑制小鼠H22肝癌的生长并诱导明显的细胞凋亡。人Ad5-PTEN-多西紫杉醇治疗荷瘤小鼠的细胞凋亡水平显著高于裸鼠Ad5-PTEN、人Ad5-PTEN或多西紫杉醇单独治疗的荷瘤小鼠。人-Ad5-PTEN-多西紫杉醇对该肿瘤模型有明显的抑制作用。与磷酸盐缓冲液对照组相比，裸露Ad5-PTEN、多西紫杉醇、Man-Ad5-PTEN和Man-Ad5-PTEN-多西紫杉醇的抑瘤率分别为48.69%、49.98%、75.88%和96.93%。结论Man-Ad5-PTEN联合化疗药物治疗肝细胞癌可能是一种有效的辅助治疗方法。
Background It has been reported that the tumor suppressor gene, PTEN, which is inactivated in many malignant tumors, plays an important role in apoptosis, cell cycle arrest, cell migration, and cell spread. For cancer gene therapy, one of the most important problems is low gene transfection efficiency. Methods In the present study, to take full advantage of adenovirus in gene expression, we prepared mannan-modified recombinant adenovirus using the PTEN gene (Man-Ad5-PTEN) and investigated the effect of Man-Ad5-PTEN combined with docetaxel (Man-Ad5-PTEN-docetaxel) on tumor growth in a murine model of hepatocellular carcinoma. Results Man-Ad5-PTEN effectively suppressed tumor growth and induced significant apoptosis of murine H22 hepatoma in vivo. Apoptosis levels in tumor-bearing mice treated with Man-Ad5-PTEN-docetaxel were significantly higher than those in tumor-bearing mice treated with naked Ad5-PTEN, Man-Ad5-PTEN, or docetaxel alone. Treatment with Man-Ad5-PTEN-docetaxel resulted in a significant inhibitory effect in this tumor model. Compared with the controls treated with phosphate-buffered solution, the tumor inhibition rate with naked Ad5-PTEN, docetaxel, Man-Ad5-PTEN, and Man-Ad5-PTEN-docetaxel was 48.69%, 49.98%, 75.88%, and 96.93%, respectively. Conclusion These results suggest that combined treatment with Man-Ad5-PTEN and other chemotherapeutic agents may be a potent adjuvant therapeutic approach for the treatment of hepatocellular carcinoma.