title: The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer.
abstract: VX680 is a potent and selective inhibitor that targets the Aurora kinase family. The p38 mitogen-activated protein kinase (MAPK) regulates a large number of cellular pathways and plays an important role in the regulation of cell survival and apoptosis. This study aimed to evaluate the effect of VX680 on cervical cancer cells and investigate whether the effects on apoptosis are enhanced by the ablation of p38 MAPK activation. The results suggested that VX680 inhibited the proliferation of cervical cancer cells by causing G2/M phase arrest and endoreduplication and that the apoptotic effect was attenuated by the activation of p38 MAPK. However, the addition of BIRB796, which is an important p38 MAPK inhibitor, effectively eliminated the expression of p-p38 and hence significantly enhanced the cell death induced by VX680 in vitro. Further study demonstrated that BIRB796 cooperated with VX680 to suppress cervical cancer cell growth in a mouse xenograft model. Taken together, our results demonstrated that VX680 induced cell cycle arrest and endoreduplication in human cervical cancer cells. Combined treatment with VX680 and BIRB796 synergistically inhibited tumor growth both in vitro and in vivo. Dual blockade of Aurora kinases and p38 MAPK is therefore a promising strategy for cervical cancer treatment.
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Mo
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Xing
authors.initials: X
authors.lastname: Hao
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Gao
authors.affiliation: a Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Pingbo
authors.initials: P
authors.lastname: Chen
mesh_terms: D000818:Animals; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D003521:Cyclopropanes; D011743:Pyrimidines; D010671:Phenylurea Compounds
chemical_list: D009281:Naphthalenes; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D048051:p38 Mitogen-Activated Protein Kinases; C484810:tozasertib; D003521:Cyclopropanes; D011743:Pyrimidines; C452139:doramapimod; D010671:Phenylurea Compounds
keywords: Apoptosis; BIRB796; VX680; cell cycle; cervical cancer; p38 MAPK