Tani Toshiaki, Tojo Naomi, Ohnishi Ken
Radiological Technology Section, QST Hospital, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
Department of Biology, Ibaraki Prefectural University of Health Sciences, Inashiki, Ibaraki 300-0394, Japan.
Oncol Lett. 2022 Mar;23(3):102. doi: 10.3892/ol.2022.13222. Epub 2022 Jan 31.
The present study examined the radiosensitization induced by a heat shock protein 90 inhibitor, N-vinylpyrrolidone (NVP)-AUY922, in CD133-positive cells in a hypoxic area of T98G spheroids. CD133-positive cells that are induced in the hypoxic microenvironment of spheroids have previously been reported to exhibit cancer stem cell-like properties. The present study used CD133-positive cells from a glioblastoma cell line (T98G) as cancer stem cell-like cells. CD133-positive and negative cells were sorted from T98G spheroids using fluorescence-activated cell sorting and used for colony formation assay. Colony formation assay results indicated that NVP-AUY922 enhanced radiosensitivity more strongly in CD133-positive cells compared with CD133-negative cells. This result showed that NVP-AUY922 was a preferential radiosensitization candidate targeting glioblastoma cancer stem cells. The mechanisms underlying radiosensitization by NVP-AUY922 are discussed in relation to the properties of cancer stem cells. Overall, HIF-1α inhibition by NVP-AUY922 may induce higher sensitization of cancer stem cells to radiation.
本研究检测了热休克蛋白90抑制剂N-乙烯基吡咯烷酮(NVP)-AUY922对T98G球体缺氧区域中CD133阳性细胞的放射增敏作用。先前有报道称,在球体缺氧微环境中诱导产生的CD133阳性细胞具有癌症干细胞样特性。本研究使用来自胶质母细胞瘤细胞系(T98G)的CD133阳性细胞作为癌症干细胞样细胞。利用荧光激活细胞分选技术从T98G球体中分选CD133阳性和阴性细胞,并用于集落形成试验。集落形成试验结果表明,与CD133阴性细胞相比,NVP-AUY922在CD133阳性细胞中增强放射敏感性的作用更强。该结果表明,NVP-AUY922是一种靶向胶质母细胞瘤癌症干细胞的优先放射增敏候选药物。结合癌症干细胞的特性讨论了NVP-AUY922放射增敏的潜在机制。总体而言,NVP-AUY922对HIF-1α的抑制作用可能会使癌症干细胞对辐射产生更高的敏感性。