COM33 suppresses carboplatin-induced epithelial-mesenchymal transition via inhibition of Twist1 in ovarian cancer  

作　　者：Zhiyang Zhou Li Jin Jian Shen Weihui Shi Yue Xu Longyun Ye Junxi Liu Jiexue Pan 

机构地区：[1]Obstetrics&Gynecology Hospital,Institute of Reproduction and Development,Fudan University,Shanghai 200011,China [2]College of Life Science,Zhejiang Chinese Medical University,Hangzhou 310053,China [3]Department of Pancreatic Surgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China [4]Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [5]Chinese Academy of Science Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province,Lanzhou Institute of Chemical Physics,Chinese Academy of Sciences,Lanzhou 730000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第1期34-42,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grant from the National Natural Science Foundation of China(No.21672225).

摘　　要：Despite favorable responses to platinum-based chemotherapy in ovarian cancer(OC),chemoresistance is still a major cause of treatment failure.Hence,we develop a novel synthetic agent,COM33,to relieve the chemoresistance caused by carboplatin.The anti-cancerous effects of the combination of COM33 and carboplatin on OC are evaluated by cell viability,wound healing,and transwell invasion assays.A mechanistic investigation is carried out by using RNA-Seq analysis and then verified by western blot analysis and immunofluorescence microscopy.The safety and efficacy in vivo are evaluated using SKOV3 tumor-bearing nude mice.Results show that the co-administration of COM33 enhances the inhibitory effects of carboplatin on cancer cell viability,migration,and invasion in vitro and tumor growth in vivo.Furthermore,COM33 suppresses the carboplatin-induced epithelialmesenchymal transition(EMT)by inhibiting the ERK signaling pathway.Additionally,we show that Twist1,the effector of the ERK signaling pathway,participates in carboplatin-induced EMT and is also inhibited by COM33.Our data show that the combination of carboplatin with COM33 is beneficial for chemotherapy against OC,which may be a potential novel anti-tumor strategy.

关 键 词：COM33 CARBOPLATIN ovarian cancer epithelial-mesenchymal transition TWIST1 

分 类 号：R737.31[医药卫生—肿瘤]