Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
Department of Medicinal Plant Resources, Andong National University, Andong, Gyeongsangbuk 36729, Republic of Korea.
Int J Mol Med. 2019 Mar;43(3):1478-1486. doi: 10.3892/ijmm.2019.4061. Epub 2019 Jan 11.
Temozolomide (TMZ) is an alkylating agent commonly used as a first‑line treatment for high‑grade glioblastoma. However, TMZ has short half‑life and frequently induces tumor resistance, which can limit its therapeutic efficiency. In the present study, it was hypothesized that combined treatment with TMZ and acteoside has synergistic effects in glioblastoma therapy. Using cell viability and wound‑healing assays, it was determined that this treatment regimen reduced cell viability and migration to a greater extent than either TMZ or acteoside alone. Following previous reports that TMZ affected autophagy in glioma cells, the present study examined the effects of TMZ + acteoside combination treatment on apoptosis and autophagy. The TMZ + acteoside combination treatment increased the cleavage of caspase‑3 and levels of B‑cell lymphoma 2 (Bcl‑2)‑associated X protein and phosphorylated p53, and decreased the level of Bcl‑2. The combination treatment increased microtubule‑associated protein 1 light chain 3 and apoptosis‑related gene expression. It was also determined that TMZ + acteoside induced apoptosis and autophagy through the mitogen‑activated protein kinase signaling pathway. These findings suggest that acteoside has beneficial effects on TMZ‑based glioblastoma therapy.
替莫唑胺(TMZ)是一种常用的烷化剂,作为高级别神经胶质瘤的一线治疗药物。然而,TMZ 的半衰期短,且常诱导肿瘤耐药,这限制了其治疗效果。在本研究中,假设 TMZ 与獐牙菜苦苷联合治疗在神经胶质瘤治疗中有协同作用。通过细胞活力和划痕愈合实验,确定该治疗方案比 TMZ 或獐牙菜苦苷单独治疗更能显著降低细胞活力和迁移。鉴于先前有报道称 TMZ 影响神经胶质瘤细胞中的自噬,本研究探讨了 TMZ+獐牙菜苦苷联合治疗对细胞凋亡和自噬的影响。TMZ+獐牙菜苦苷联合治疗增加了半胱氨酸天冬氨酸蛋白酶-3 的裂解和 B 细胞淋巴瘤 2(Bcl-2)相关 X 蛋白和磷酸化 p53 的水平,并降低了 Bcl-2 的水平。联合治疗增加了微管相关蛋白 1 轻链 3 和凋亡相关基因的表达。还确定 TMZ+獐牙菜苦苷通过丝裂原活化蛋白激酶信号通路诱导细胞凋亡和自噬。这些发现表明獐牙菜苦苷对基于 TMZ 的神经胶质瘤治疗有有益作用。