title: Down-regulation of IGF-1R expression inhibits growth and enhances chemosensitivity of endometrial carcinoma in vitro.
abstract: The type-1 insulin-like growth factor receptor (IGF-1R) is over-expressed by endometrial carcinoma, level of IGF-1R has been correlated with tumor progression, and high IGF-1R expression has been found to be an important prognostic factor. In the study, we used lentivirus-mediated shRNA targeting IGF-1R to silence its expression, then assessed the effect of down-regulation of this receptor on cell growth and chemosensitivity to cisplatin. Lentivirus-mediate shRNA was designed and transfected to the endometrial carcinoma HEC-1B cell. The IGF-1R mRNA and related protein expression, cell proliferation ability, cell apoptosis, and cell cycle change were detected. Cell proliferation inhibition rates, cell apoptosis, and level of cleaved caspase-9 were measured in various concentrations of cisplatin. The mRNA and protein level of IGF-1R, and the phosphorylated protein p-Akt, p-Erk were all suppressed after transfection. Cell proliferation was inhibited in successive five days after transfection, the highest inhibition rate was 43.28 ± 3.55% on day 5. After transfection, 24.96 ± 1.05% cells were in G(2)/M phase, and cell apoptotic rate increased from 10.66 ± 0.08 to 19.92 ± 1.34%. In various concentrations of cisplatin, transfected cells proliferation was significantly inhibited which made the IC50 value drop from 21.85 uM to 10.58 uM. Incubation with different concentrations of cisplatin for 48 h, cells apoptotic rate increased to 41.92 ± 2.5, 31.13 ± 2.76, 22.21 ± 4.63%, respectively, which was accompanied with increased cleaved caspase-9 expression. Lentivirus-mediated shRNA targeting IGF-1R has the potential to develop as a clinical treatment method in advanced and chemoresistant endometrial carcinoma.
authors: Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, 600 TianHe Road, Guangzhou 510630, People's Republic of China.
authors: Shanrong
authors: S
authors: Shu
authors: Yuebo
authors: Y
authors: Yang
authors: Xiaomao
authors: X
authors: Li
authors: Tian
authors: T
authors: Li
authors: Yu
authors: Y
authors: Zhang
authors: Chengfang
authors: C
authors: Xu
authors: Changyan
authors: C
authors: Liang
authors: Xiaoyun
authors: X
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D020128:Inhibitory Concentration 50; D016086:Lentivirus / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002945:Cisplatin