Novosibirsk State University, Novosibirsk, Russia.
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.
Anticancer Res. 2019 Nov;39(11):6073-6086. doi: 10.21873/anticanres.13815.
BACKGROUND/AIM: Oncolytic adenoviruses are promising therapeutic agents against both the bulk of tumor cells and cancer stem cells. The present study intended to test the oncolytic capability of adenovirus serotype 6 (Ad6), which has a lower seroprevalence and hepatotoxicity relatively to adenovirus 5 (Ad5), against the glioblastoma and its cancer stem cells.
Oncolytic efficacy of Ad6 was compared to widespread Ad5 both in vitro and in vivo, using the U87 and U251 human glioblastoma cell lines and subcutaneously transplanted U87 cells in SCID mice, respectively.
Ad6 had a dose-dependent cytotoxicity toward glioblastoma cells in vitro and its intratumoral injections lead to a significant (p<0.05) decrease in volume of U87 xenografts, similarly to Ad5. Based on the innate capability of glioblastoma cancer stem cells to internalize a fluorescent-labeled double-stranded DNA probe, the spatial localization of these cells was estimated and it was shown that the number of cancer stem cells tended to decrease under adenovirus therapy as compared to the control group.
Ad6 was shown to be a promising agent for treating glioblastomas.
背景/目的：溶瘤腺病毒是一种有前途的治疗剂，可用于治疗肿瘤细胞和癌症干细胞。本研究旨在测试血清型 6 型腺病毒（Ad6）的溶瘤能力，与血清型 5 型腺病毒（Ad5）相比，Ad6 的血清阳性率和肝毒性较低，针对脑胶质瘤及其癌症干细胞。
使用 U87 和 U251 人胶质母细胞瘤细胞系和皮下移植的 U87 细胞在 SCID 小鼠中，分别在体外和体内比较 Ad6 和广泛使用的 Ad5 的溶瘤功效。
Ad6 在体外对胶质母细胞瘤细胞具有剂量依赖性的细胞毒性，其肿瘤内注射导致 U87 异种移植物的体积显著（p<0.05）减少，与 Ad5 相似。基于胶质瘤癌症干细胞内化荧光标记双链 DNA 探针的固有能力，估计这些细胞的空间定位，并表明与对照组相比，癌症干细胞的数量在腺病毒治疗下趋于减少。
Ad6 被证明是治疗脑胶质瘤的一种有前途的药物。
