title: Combination of rituximab and mammalian target of rapamycin inhibitor everolimus (RAD001) in diffuse large B-cell lymphoma.
abstract: Abstract We evaluated the efficacy of the anti-CD20 monoclonal antibody rituximab in combination with the mammalian target of rapamycin (mTOR) inhibitor everolimus for treating diffuse large B-cell lymphoma (DLBCL). The combination of rituximab and everolimus was more effective for inhibiting cell growth compared with single-agent therapy. An increase in G0/G1 cell cycle arrest and an increased population of cells in apoptosis were observed in the combination treatment group. The addition of rituximab reduced the overexpression of p-AKT caused by the negative feedback loop of everolimus and had an enhanced effect on inhibition of mTOR signaling, thus providing a rationale for this synergistic effect. Furthermore, combination treatment was also more effective than treatment with either agent alone for inhibiting the growth of DLBCL xenografts. Our study provides preclinical evidence and a theoretical basis for combination therapy with rituximab and everolimus in DLBCL.
authors.affiliation: Department of Laboratory Medicine, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Zi-Zhen
authors.initials: ZZ
authors.lastname: Xu
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Wang
authors.forename: Wan-Bin
authors.initials: WB
authors.lastname: Fu
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Wang
authors.forename: Zhi-Yin
authors.initials: ZY
authors.lastname: Liu
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Chen
authors.forename: Pei
authors.initials: P
authors.lastname: Guo
authors.forename: Jun-Min
authors.initials: JM
authors.lastname: Li
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D000068338:Everolimus; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D000069283:Rituximab; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus