Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Mol Biol Rep. 2024 Nov 17;51(1):1161. doi: 10.1007/s11033-024-10074-x.
Chronic Myeloid Leukemia (CML), accounting for 15-20% of adult leukemia cases, is marked by the Philadelphia chromosome, resulting from the t(9;22)(q34;q11) translocation. This leads to uncontrolled cell proliferation and survival. Imatinib therapy lowers BCR-ABL levels, influencing telomere-associated proteins and increasing telomerase accessibility, indirectly boosting its activity. This study investigates the effects of MST-312 and imatinib, both individually and combined, on a CML cell line.
The K562 cells were subjected to different doses of MST-312 and imatinib, including four combination concentrations. Cell viability and metabolic activity were measured using trypan blue and MTT assays at 24-, 36-, and 48-h post-treatment. Flow cytometry (AnnexinV/PI) assessed cell apoptosis after 36 h of treatment with MST-312 and imatinib, both individually and in combination. The expression levels of Bax, Bcl-2, hTERT, P21, P53, and c-Myc were determined via qRT-PCR.
Both MST-312 and imatinib independently reduced cell viability in a dose- and time-dependent manner. Their combination further decreased cell viability compared to monotherapy. Treatment of K562 cells with MST-312 and imatinib for 36 h increased Bax expression and the Bax/Bcl-2 ratio while decreasing Bcl-2 expression. Combined treatment significantly reduced hTERT ansd P21 gene expression compared to imatinib alone.
The combination of MST-312 and imatinib shows potential as a CML therapy. However, further research and clinical trials are necessary to validate these findings and determine their clinical relevance.
慢性髓性白血病（CML）占成人白血病病例的 15-20%，其特征为费城染色体，由 t(9;22)(q34;q11)易位导致。这导致细胞不受控制地增殖和存活。伊马替尼治疗降低了 BCR-ABL 水平，影响端粒相关蛋白并增加端粒酶的可及性，间接提高其活性。本研究调查 MST-312 和伊马替尼单独和联合对 CML 细胞系的影响。
K562 细胞接受不同剂量的 MST-312 和伊马替尼，包括四个组合浓度。在治疗后 24、36 和 48 小时使用台盼蓝和 MTT 测定法测量细胞活力和代谢活性。在 36 小时的 MST-312 和伊马替尼单独和联合治疗后，通过流式细胞术（AnnexinV/PI）评估细胞凋亡。通过 qRT-PCR 测定 Bax、Bcl-2、hTERT、P21、P53 和 c-Myc 的表达水平。
MST-312 和伊马替尼均独立地以剂量和时间依赖的方式降低细胞活力。它们的组合与单药治疗相比进一步降低了细胞活力。用 MST-312 和伊马替尼处理 K562 细胞 36 小时增加了 Bax 表达和 Bax/Bcl-2 比值，同时降低了 Bcl-2 表达。与单独使用伊马替尼相比，联合治疗显著降低了 hTERT 和 P21 基因的表达。
MST-312 和伊马替尼的联合具有作为 CML 治疗的潜力。然而，需要进一步的研究和临床试验来验证这些发现并确定其临床相关性。
