title: CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells.
abstract: Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types of cancer cells. Whether CD147 alters the effect of trastuzumab on HER2-positive breast cancer cells has not been previously reported. Our study confirmed that CD147 suppression enhances the effects of trastuzumab both in vitro and in vivo. CD147 suppression increased the inhibitory rate of trastuzumab and cell apoptosis in SKBR3, BT474, HCC1954 and MDA-MB453 cells compared with the controls. Furthermore, CD147 knockdown increased expression of cleaved Caspase-3/9 and poly (ADP-ribose) polymerase (PARP) and decreased both mitogen-activated protein kinase (MAPK) and Akt phosphorylation in the four cell lines. In an HCC1954 xenograft model, trastuzumab achieved greater suppression of tumor growth in the CD147-knockdown group than in the shRNA negative control (NC) group. These data indicated that enhancement of the effect of trastuzumab on HER2-positive cells following CD147 knockdown might be attributed to increased apoptosis and decreased phosphorylation of signaling proteins. CD147 may be a key protein for enhancing the clinical efficacy of trastuzumab.
authors.affiliation: Central Laboratory, Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xiong
authors.affiliation: The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510630, P.R.China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Pathology, Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Haoyong
authors.initials: H
authors.lastname: Ning
authors.affiliation: Central Laboratory, Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Wu
authors.affiliation: Central Laboratory, Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Kaifei
authors.initials: K
authors.lastname: Fu
authors.affiliation: Central Laboratory, Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Surgery, Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510630, P.R.China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Central Laboratory, Navy General Hospital, Beijing 100048, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology; D017209:Apoptosis; D051926:Basigin / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab / Q000494:pharmacology*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D051926:Basigin; D011065:Poly(ADP-ribose) Polymerases; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C497886:BSG protein, human; C508053:ERBB2 protein, human
keywords: CD147; HER2; antibody drug resistance/sensitivity; breast cancer; trastuzumab efficacy