title: Adipocytes secreted leptin is a pro-tumor factor for survival of multiple myeloma under chemotherapy.
abstract: Accumulating evidences have shown that adipokines secreted from adipocytes contributes to tumor development, especially leptin. However, underlying mechanisms remain unclear. This study aims to explore the effect of leptin on development and chemoresistance in multiple myeloma cells and the potential mechanism. Analysis of levels of adipokines including leptin and adiponectin in 28 multiple myeloma patients identified significantly higher leptin compared with 28 normal controls(P < 0.05), and leptin level was positively correlated with clinical stage, IgG, ER, and ß2MG. Next, by using co-culture system of myeloma and adipocytes, and pharmacologic enhancement of leptin, we found that increased growth of myeloma cells and reduced toxicity of bortezomib were best observed at 50 ng/ml of leptin, along with increased expression of cyclinD1, Bcl-2 and decreased caspase-3 expression. We also found that phosphorylated AKT and STAT3 but not the proteins expression reached peak after 1h and 6h treatment of leptin, respectively. By using AG490, an agent blocking the phosphorylation of AKT and ERK, the proliferation of myeloma cells was inhibited, as well as the phosphorylation of AKT and STAT3, even adding leptin. Taken together, our study demonstrated that up-regulated leptin could stimulate proliferation of myeloma and reduce the anti-tumor effect of chemotherapy possibly via activating AKT and STAT3 pathways, and leptin might be one of the potential therapeutic targets for treating myeloma.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Oncology, Remmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: De-Dong
authors.initials: DD
authors.lastname: Cao
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qiu-Bai
authors.initials: QB
authors.lastname: Li
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Mei
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D020738:Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: adipokines; chemotherapy; leptin; multiple myeloma