Effects and mechanism of arsenic trioxide in combination with rmhTRAIL in multiple myeloma.
The anti-tumor potential of arsenic trioxide (ATO) and recombinant mutant human TRAIL (rmhTRAIL) has been confirmed in various kinds of tumors. However, the effects and mechanism of the two drugs in combination in multiple myeloma (MM) have not been established. In this study, we evaluated the proliferation inhibition and apoptosis induction effects of ATO and rmhTRAIL as single agents and in combination on the MM cell lines RPMI8226 and U266. Then, we used high-performance liquid chromatography and mass spectrometry to find differentially expressed proteins before and after drug treatment and to analyze the mechanism underlying the effect of ATO and rmhTRAIL on MM cells. Results indicated that ATO and rmhTRAIL had synergistic or additive effects on proliferation inhibition and apoptosis induction in MM cells, and the mechanism underlying the two-drug combination might involve regulation of the expression of several proteins affected by ATO and rmhTRAIL. Our study provides evidence of a potential new combination treatment strategy for MM.
Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Department of Hematology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Hebing
H
Zhou
Department of Hematology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Jinqing
J
Li
Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Yuan
Y
Jian
Department of Hematology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Tingting
T
Chen
School of Life Sciences, Tsinghua University, Beijing, China.
Haiteng
H
Deng
Department of Hematology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Juan
J
Zhang
Department of Hematology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Hui
H
Zeng
Department of Hematology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Zhijuan
Z
Shan
Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. Electronic address: xybxx@ccmu.edu.cn.
Wenming
W
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D009101:Multiple Myeloma / Q000473:pathology*; D010087:Oxides / Q000633:toxicity*; D011994:Recombinant Proteins / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
D001152:Arsenicals; D010087:Oxides; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D000077237:Arsenic Trioxide