Namkaew Jirapat, Jaroonwitchawan Thiranut, Rujanapun Narawadee, Saelee Jantip, Noisa Parinya
Laboratory of Cell-Based Assays and Innovations, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima, 30000, Thailand.
In Vitro Cell Dev Biol Anim. 2018 Oct;54(9):629-639. doi: 10.1007/s11626-018-0288-9. Epub 2018 Aug 22.
Neuroblastoma is the most common cancer of the sympathetic nervous system in children. Here, the influences of curcumin on survival, apoptosis, migration, and its combined effects with doxorubicin were investigated in SH-SY5Y cells by cell survival assay, flow cytometry, migration assays, and RT-PCR. Curcumin inhibited SH-SY5Y cell growth and induced apoptosis in dose- and time-dependent manners. This apoptotic induction relied on the upregulation of p53 and p21. Moreover, the treatment of curcumin for 24 h significantly suppressed cell migration, together with the downregulation of matrix metalloproteinase-2 (MMP-2) and upregulation of tissue inhibitor of metalloproteinases-1 (TIMP-1). The combination of curcumin augmented the anticancer activity of doxorubicin and significantly induced apoptosis. Pretreatment with curcumin increased the fraction of doxorubicin-induced apoptotic cells from 21.76 ± 0.50 to 57.74 ± 2.68%. Co-treatment with doxorubicin plus curcumin further inhibited 3D tumor migration. Altogether, the results suggest that curcumin suppresses growth and migration of SH-SY5Y cells and enhances the anticancer activity of doxorubicin. The addition of curcumin to therapeutic regimens may be promising for the treatment of neuroblastomas if a number of problems related to its in vivo bioavailability can be resolved. Graphical abstract ᅟ.
神经母细胞瘤是儿童交感神经系统最常见的癌症。在此，通过细胞存活测定、流式细胞术、迁移测定和逆转录聚合酶链反应，研究了姜黄素对SH-SY5Y细胞存活、凋亡、迁移的影响及其与阿霉素的联合作用。姜黄素以剂量和时间依赖性方式抑制SH-SY5Y细胞生长并诱导凋亡。这种凋亡诱导依赖于p53和p21的上调。此外，姜黄素处理24小时可显著抑制细胞迁移，同时下调基质金属蛋白酶-2（MMP-2）并上调金属蛋白酶组织抑制剂-1（TIMP-1）。姜黄素联合用药增强了阿霉素的抗癌活性并显著诱导凋亡。用姜黄素预处理可使阿霉素诱导的凋亡细胞比例从21.76±0.50%增加到57.74±2.68%。阿霉素与姜黄素联合处理进一步抑制了3D肿瘤迁移。总之，结果表明姜黄素可抑制SH-SY5Y细胞的生长和迁移，并增强阿霉素的抗癌活性。如果与姜黄素体内生物利用度相关的一些问题能够得到解决，那么在治疗方案中添加姜黄素可能有望用于神经母细胞瘤的治疗。图形摘要ᅟ。
