4.6 Article

Down-regulation of IGF-1R expression inhibits growth and enhances chemosensitivity of endometrial carcinoma in vitro

Journal

MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 353, Issue 1-2, Pages 225-233

Publisher

SPRINGER
DOI: 10.1007/s11010-011-0790-9

Keywords

The type-1 insulin-like growth factor receptor; Chemosensitivity; Endometrial carcinoma; Lentivirus; RNA interference

Categories

Funding

  1. Science and Technology Plan Project of Guang Dong Province [2007B 030502014, 00429391120223052]
  2. National Nature Science Foundation of China [30772332]

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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.

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