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Archive > Volume 21 Issue 2 > 2014,21(2):136-141. DOI:10.3872/j.issn.1007-385X.2014.02.004 Prev Next
Basic Research
Combination anti-tumor effects of an anti-IGF-ⅠR antibody and cisplatin on the growth of ovarian carcinoma cells and xenografts
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Abstract:
Objective : To investigate the antitumor effects of an monoclonal antibody (mAb) against type 1 insulin-like growth factor receptor (IGF-ⅠR) 4F2 and cisplatin, either each alone or both in combination, on the growth of ovarian carcinoma cells and xenografts. Methods: Four ovarian carcinoma cell lines (CAOV3, ES2, SKOV3 and Hey cells) were treated with a mAb against human IGF-IR 4F2 and cisplatin, each alone or both in combination. Levels of total IGF-IR protein in CAOV3, ES2, SKOV3 and Hey cells and phosphorylated IGF-IR protein in CAOV3 and SKOV3 cells were analyzed by Western blotting before and after treatments. The binding specificity of the IGF-IR 4F2 antibody to the four types ovarian carcinoma cells was assessed by flow cytometry. The inhibitory effects of treatments on the growth of ovarian cancer cells was assessed with the CCK-8 assay in vitro. To evaluate these effects in vivo, nude mice were injected with SKOV3 and CAOV3 cells, followed by drug treatment (i.e., the IGF-IR 4F2 antibody and 0.2 μg/ml cisplatin, each alone or both in combination). PBS served as a negative control. The animals were then sacrificed and their ovarian tumor size was examined. Accordingly, rates of the treatment-induced tumor growth inhibition were calculated. Results: IGF-ⅠR protein was detected in CAOV3, ES2 and SKOV3 cells. IGF-IR 4F2 antibody bound specifically to these cells and resulted in a significant decrease in IGF-IR phosphorylation (P<0.05). The combined use of the IGF-IR 4F2 antibody and cisplatin was significantly more effective than the separate use of these two drugs in inhibiting proliferation in both SKOV3 cells ([47.4±3.1]% vs [5.3±0.6]% and [30.5±4.1]%,P<0.05) and CAOV3 cells ([51.6±2.3\]% vs [8.2±1.8]% and, [28.9±2.3]%, P<0.05). In vivo, the IGF-IR 4F2 antibody and cisplatin in combination had significantly higher inhibition rates than the two drugs each by itself on tumor growth in both mice injected with SKOV3 cells([87.3±3.1]% vs[41.6±4.9]% and [28.9±5.5]%,P<0.01) and mice injected with CAOV3 cells ([86.6±3.5]% vs [42.1±7.7]%, [32.7±4.1]%, P<0.01). Conclusion: The tested anti-human IGF-IR 4F2 mAb can bind specifically to IGF-ⅠR-positive ovarian carcinoma cells and has a synergistic inhibitory effect on the growth of ovarian carcinoma cells both in vitro and vin vivo when used in combination with cisplatin.
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Project Supported:
Project supported by the Innovation Foundation for Master and Doctor of the Cancer Institute of Shanghai （No. SB11-03），the Specialized Research Foundation for the Doctoral Program of Higher Education（No. 20100073120092）, and the Key Basic Research Program from Science and Technology Commission of Shanghai （No. 12JC1408300）
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