Transduction and oncolytic profile of a potent replication-competent adenovirus 11p vector (RCAd11pGFP) in colon carcinoma cells.
Transduction and oncolytic profile of a potent replication-competent adenovirus 11p vector (RCAd11pGFP) in colon carcinoma cells.
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DOI：
10.1371/journal.pone.0017532
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发表时间：
2011-03-24
期刊：
影响因子：
3.7
通讯作者：
Mei YF
中科院分区：
文献类型：
--
作者：
Silver J;Mei YF
复制型腺病毒5型（Ad5）载体有望成为比其复制缺陷型载体更有效的基因递送载体，并且能够靶向CD46的嵌合Ad5载体比具有天然纤维的Ad5载体更有效。虽然已经使用了几种策略来改善基因转导和溶瘤，无论是通过修改它们的向性或提高它们的复制能力，一些肿瘤细胞仍然是相对难感染嵌合Ad5。载体的溶瘤作用在某些肿瘤中是明显的，但在其他肿瘤中不是。在这里，我们报告的复制型腺病毒11 p载体（RCAd11pGFP）在结肠癌细胞的生物学和溶瘤概况。CD46在所有研究的细胞中大量表达;然而，RCAd11pGFP的转导效率各不相同。RCAd11pGFP有效地转导HT-29、HCT-8和LS 174T细胞，但其转导源自肺中结肠癌转移的T84细胞的效率较低。有趣的是，RCAd11p在T84细胞中的复制速度比在HCT-8和LS 174T细胞中更快，并且与HT-29细胞一样快。细胞毒性和增殖试验表明，RCAd11pGFP在HT29和T84细胞中具有最高的细胞杀伤活性，后者也表达最高水平的癌胚抗原（CEA）家族的糖蛋白。体内实验显示，与未处理的对照组相比，用RCAd11pGFP或Ad11pwt处理的异种移植小鼠中T84和HT-29肿瘤的生长受到显著抑制。因此，RCAd11pGFP对结肠癌细胞具有强的细胞毒作用。
Replication-competent adenovirus type 5 (Ad5) vectors promise to be more efficient gene delivery vehicles than their replication-deficient counterparts, and chimeric Ad5 vectors that are capable of targeting CD46 are more effective than Ad5 vectors with native fibers. Although several strategies have been used to improve gene transduction and oncolysis, either by modifying their tropism or enhancing their replication capacity, some tumor cells are still relatively refractory to infection by chimeric Ad5. The oncolytic effects of the vectors are apparent in certain tumors but not in others. Here, we report the biological and oncolytic profiles of a replication-competent adenovirus 11p vector (RCAd11pGFP) in colon carcinoma cells. CD46 was abundantly expressed in all cells studied; however, the transduction efficiency of RCAd11pGFP varied. RCAd11pGFP efficiently transduced HT-29, HCT-8, and LS174T cells, but it transduced T84 cells, derived from a colon cancer metastasis in the lung, less efficiently. Interestingly, RCAd11p replicated more rapidly in the T84 cells than in HCT-8 and LS174T cells and as rapidly as in HT-29 cells. Cell toxicity and proliferation assays indicated that RCAd11pGFP had the highest cell-killing activities in HT29 and T84 cells, the latter of which also expressed the highest levels of glycoproteins of the carcinoma embryonic antigen (CEA) family. In vivo experiments showed significant growth inhibition of T84 and HT-29 tumors in xenograft mice treated with either RCAd11pGFP or Ad11pwt compared to untreated controls. Thus, RCAd11pGFP has a potent cytotoxic effect on colon carcinoma cells.
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影响因子：
82.9
作者：
Gaggar, A;Shayakhmetov, DM;Lieber, A
通讯作者：
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