In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines.
In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines.
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大黄素35衍生物对多发性骨髓瘤细胞系细胞毒活性的体外研究
DOI：
10.1155/2021/6682787
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Zheng J;Chen Y;Zheng Z;Chen Y;Chai Y;Wang W;Asakawa T;Hu J
背景硼替佐米用于治疗多发性骨髓瘤（MM）;然而，它具有相当大的副作用。大黄素已被报道对MM细胞系表现出抑制作用。我们研究了大黄素衍生物大黄素35（E35）的疗效，使用U266和MM 1 s细胞系治疗MM，以及硼替佐米和E35联合治疗的疗效。方法采用MTT法观察E35对MM细胞生长的影响。采用Annexin V/PI染色法观察其对细胞凋亡的影响。检测了包括胱天蛋白酶家族在内的糖尿病相关基因的表达。通过检测Akt/mTOR/4 EBP 1信号通路相关蛋白的表达来研究硼替佐米和E35组合的功效。结果E35通过诱导细胞凋亡抑制U266和MM 1 s细胞的生长。此外，E35下调了糖尿病相关基因的表达，并抑制了Akt/mTOR/4 EBP 1信号通路相关基因的磷酸化，因此与硼替佐米表现出协同作用。所有观察到的效应均呈剂量依赖性。结论E35对MM细胞具有蛋白水平的细胞毒作用。因此，E35，特别是与硼替佐米联合，可能被认为是MM的有希望的治疗方法;然而，这需要进一步的体内研究。
Background Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35. Methods MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins. Results We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent. Conclusion The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation in vivo.
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用FDA批准的利托那韦和二甲双胍靶向多发性骨髓瘤的代谢可塑性。
DOI：
10.1158/1078-0432.ccr-14-1088
发表时间：
2015-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dalva-Aydemir S;Bajpai R;Martinez M;Adekola KU;Kandela I;Wei C;Singhal S;Koblinski JE;Raje NS;Rosen ST;Shanmugam M
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Shanmugam M
影响因子：
20.3
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Lu, Jing;Zavorotinskaya, Tatiana;Garcia, Pablo D.
通讯作者：
Garcia, Pablo D.
影响因子：
20.3
作者：
Bahlis, Nizar J.;Sutherland, Heather;Chen, Christine
通讯作者：
Chen, Christine
敲低 c-Met 通过抑制 Akt/mTOR 活性增强人多发性骨髓瘤 U266 细胞对硼替佐米的敏感性
影响因子：
2.8
作者：
Que, Wenzhong;Chen, Junmin;Jiang, Danrong
通讯作者：
Jiang, Danrong
影响因子：
--
作者：
Ma JW;Hung CM;Lin YC;Ho CT;Kao JY;Way TD
通讯作者：
Way TD