Weng Guangyang, Zeng Yingjian, Huang Jingya, Fan Jiaxin, Guo Kunyuan
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China.
Department of Hematology, Jiangmen Wuyi Traditional Chinese Medicine Hospital, Jiangmen 529000, China.
Biomed Res Int. 2015;2015:630397. doi: 10.1155/2015/630397. Epub 2015 Oct 18.
Leukemia relapse and nonrecurrence mortality (NRM) due to leukemia stem cells (LSCs) represent major problems following hematopoietic stem cell transplantation (HSCT). To eliminate LSCs, the sensitivity of LSCs to chemotherapeutic agents used in conditioning regimens should be enhanced. Curcumin (CUR) has received considerable attention as a result of its anticancer activity in leukemia and solid tumors. In this study, we investigated the cytotoxic effects and underlying mechanisms in leukemia stem-like KG1a cells exposed to busulfan (BUS) and CUR, either alone or in combination. KG1a cells exhibiting BUS-resistance demonstrated by MTT and annexin V/propidium iodide (PI) assays, compared with HL-60 cells. CUR induced cell growth inhibition and apoptosis in KG1a cells. Apoptosis of KG1a cells was significantly enhanced by treatment with CUR+BUS, compared with either agent alone. CUR synergistically enhanced the cytotoxic effect of BUS. Seven apoptosis-related proteins were modulated in CUR- and CUR+BUS-treated cells analyzed by proteins array analysis. Importantly, the antiapoptosis protein survivin was significantly downregulated, especially in combination group. Suppression of survivin with specific inhibitor YM155 significantly increased the susceptibility of KG1a cells to BUS. These results demonstrated that CUR could increase the sensitivity of leukemia stem-like KG1a cells to BUS by downregulating the expression of survivin.
白血病干细胞（LSCs）导致的白血病复发和非复发死亡率（NRM）是造血干细胞移植（HSCT）后的主要问题。为了消除LSCs，应提高LSCs对预处理方案中使用的化疗药物的敏感性。姜黄素（CUR）因其在白血病和实体瘤中的抗癌活性而受到广泛关注。在本研究中，我们研究了单独或联合使用白消安（BUS）和CUR对白血病干细胞样KG1a细胞的细胞毒性作用及其潜在机制。与HL-60细胞相比，MTT和膜联蛋白V/碘化丙啶（PI）检测显示KG1a细胞表现出对BUS耐药。CUR诱导KG1a细胞的生长抑制和凋亡。与单独使用任何一种药物相比，CUR+BUS处理显著增强了KG1a细胞的凋亡。CUR协同增强了BUS的细胞毒性作用。通过蛋白质阵列分析，在CUR和CUR+BUS处理的细胞中检测到七种凋亡相关蛋白的表达受到调节。重要的是，抗凋亡蛋白生存素显著下调，尤其是在联合治疗组。用特异性抑制剂YM155抑制生存素可显著增加KG1a细胞对BUS的敏感性。这些结果表明，CUR可通过下调生存素的表达增加白血病干细胞样KG1a细胞对BUS的敏感性。
