Miri Zahra Sadat, Bagheri Hossein, Amani Alireza, Karami Hadi
Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.
Department of Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Int J Mol Cell Med. 2025;14(1):552-566. doi: 10.22088/IJMCM.BUMS.14.1.552.
The resistance of tumor cells to ABT-737 can be attributed to alterations in the equilibrium of Bcl-2 family proteins. In this study, the effect of curcumin on the Mcl-1expression and the sensitivity of glioblastoma cells to ABT-737 were examined. Trypan blue assay and colony formation assay were performed to explore the effects of treatments on cell proliferation. MTT assay was performed to measure cytotoxicity. Cell migration was determined using a wound healing assay. Cell apoptosis was measured by Hoechst 33342 staining, ELISA cell death, and caspase-3 activity assay. The expression levels of Mcl-1 mRNA were also tested by qRT-PCR. Our results revealed that combination therapy significantly lowered the IC value and synergistically decreased the colony formation and migration, cell survival and growth of glioblastoma cells compared with curcumin or ABT-737 alone. Treatment with curcumin clearly inhibited the expression of Mcl-1 mRNA. Moreover, suppression of Mcl-1 mRNA by curcumin was associated with enhancement of apoptosis induced by ABT-737. In conclusion, curcumin has the ability to inhibit the cell proliferation and migration, and activate the intrinsic pathway of apoptosis. Moreover, it can enhance the sensitivity of glioblastoma cells to ABT-737 by suppressing the expression of Mcl-1.
肿瘤细胞对ABT-737的耐药性可归因于Bcl-2家族蛋白平衡的改变。在本研究中，检测了姜黄素对Mcl-1表达的影响以及胶质母细胞瘤细胞对ABT-737的敏感性。进行台盼蓝试验和集落形成试验以探究处理对细胞增殖的影响。进行MTT试验以测量细胞毒性。使用伤口愈合试验测定细胞迁移。通过Hoechst 33342染色、ELISA细胞死亡和caspase-3活性试验测量细胞凋亡。还通过qRT-PCR检测Mcl-1 mRNA的表达水平。我们的结果显示，与单独使用姜黄素或ABT-737相比，联合治疗显著降低了IC值，并协同降低了胶质母细胞瘤细胞的集落形成和迁移、细胞存活及生长。姜黄素处理明显抑制了Mcl-1 mRNA的表达。此外，姜黄素对Mcl-1 mRNA的抑制与ABT-737诱导的凋亡增强相关。总之，姜黄素具有抑制细胞增殖和迁移、激活凋亡内在途径的能力。此外，它可通过抑制Mcl-1的表达增强胶质母细胞瘤细胞对ABT-737的敏感性。
