title: Overexpression of osteopontin promotes resistance to cisplatin treatment in HCC.
abstract: Osteopontin (OPN) is a multi-functional cytokine involved in cell survival, migration and adhesion. Increasing evidence has elucidated its role in tumorigenesis, progression and metastasis. However, the role of OPN in chemoresistance of human hepatocellular carcinoma (HCC) has not yet been clarified. In the present study, we examined the expression of OPN in human HCC samples before and after cisplatin-treatment, the results showed that OPN was significantly increased in cisplatin-resistant specimens. We then studied the effect of cisplatin on OPN expression in HCC cells, after exposure to cisplatin, the expression of OPN in HCC cells was elevated compared to control cells. We also found that PI3K/AKT signaling pathway was also activated by cisplatin and this effect was induced by the OPN pathway. To study the effect of OPN on chemoresistance, HCC cells were treated with cisplatin along with OPN. Incubation with OPN enchanced the chemoresistance of HCC cells to cisplatin. In contrast, blockage of OPN pathway promoted the chemosensitivity of HCC cells to cisplatin. Our results suggest that OPN enhanced chemoresistance of cisplatin in HCC cells by activating PI3K/AKT signaling pathway, blocking the OPN pathway might be a novel way to overcome the disease.
authors.affiliation: Department of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University School of Medicine, Jian, Shandong 250000, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Ding
authors.affiliation: Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University School of Medicine, Jian, Shandong 250000, P.R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
authors.forename: Jiguang
authors.initials: J
authors.lastname: Yu
authors.affiliation: Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
authors.forename: Xiangzhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
authors.forename: Youde
authors.initials: Y
authors.lastname: Liu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000235:genetics; D053495:Osteopontin / Q000096:biosynthesis* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D002945:Cisplatin