Enhanced suppression of prostate tumor growth by combining C-CAM1 gene therapy and angiogenesis inhibitor TNP-470.
Enhanced suppression of prostate tumor growth by combining C-CAM1 gene therapy and angiogenesis inhibitor TNP-470.
复制标题
通过结合 C-CAM1 基因疗法和血管生成抑制剂 TNP-470 增强对前列腺肿瘤生长的抑制。
DOI：
10.1097/00001813-200208000-00009
复制
发表时间：
2002
影响因子：
2.3
通讯作者：
Lin,Sue-Hwa
中科院分区：
文献类型：
--
作者：
Pu,Yeong-Shiau;Do,Kim-Anh;Luo,Weiping;Logothetis,ChristopherJ;Lin,Sue-Hwa
我们之前已经证明，基于 C-CAM1 的基因治疗可以有效抑制裸鼠异种移植模型中的前列腺肿瘤生长。在这项研究中，我们在异种移植肿瘤模型中检查了基于 C-CAM1 的疗法和 TNP-470（一种有效的血管生成抑制剂）相结合对前列腺癌的影响。通过微量培养四唑测定测定 Ad-C-CAM1（含有 C-CAM1 cDNA 的重组腺病毒）和 TNP-470 对 DU145 细胞的体外直接细胞毒作用。在 DU145 异种移植肿瘤模型中研究了任一药物单独的体内抗肿瘤作用。用Ad-C-CAM1或对照病毒以5或10的感染复数(moi)感染细胞，48小时后接种到裸鼠上。接种后 15、17 和 19 天给予 TNP-470（0、17 或 35 mg/kg）。进行体内联合治疗以确定是否存在协同抗肿瘤作用。 Ad-C-CAM1 和对照病毒在体外对 DU145 的毒性极小。 Ad-C-CAM1 或 TNP-470 对异种移植肿瘤生长有明显的剂量依赖性抑制。通过中值效应分析，两种药物的组合产生了强大的协同抗肿瘤作用，与单独治疗相比，显着的肿瘤抑制表明了这一点。这种新策略可能对前列腺癌的治疗具有临床意义。
We have previously shown that C-CAM1-based gene therapy effectively suppressed prostate tumor growth in nude mice xenograft models. In this study, we examined the effects of combining C-CAM1-based therapy and TNP-470, a potent angiogenesis inhibitor, on prostate cancer in a xenografted tumor model. The direct cytotoxic effects of Ad-C-CAM1 (recombinant adenovirus containing C-CAM1 cDNA) and TNP-470 on DU145 cells in vitro were determined by microculture tetrazolium assay. The in vivo antitumor effects of either agent alone were studied in a DU145 xenografted tumor model. Cells were infected with Ad-C-CAM1 or the control virus at multiplicities of infection (moi) of 5 or 10 and then inoculated onto nude mice 48 h later. TNP-470 (0, 17 or 35 mg/kg) was given 15, 17 and 19 days after inoculation. Combined treatments in vivo were carried out to determine whether there were synergistic antitumor effects. Both Ad-C-CAM1 and the control virus were minimally toxic to DU145 in vitro. There was evident dose-dependent suppression of xenografted tumor growth by either Ad-C-CAM1 or TNP-470. By the median-effect analysis, combination of the two agents generated strong synergistic antitumor effects as shown by marked tumor suppression as compared to either treatment alone. The novel strategy may have clinical implications for the treatment of prostate cancer.