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A monoclonal antibody targeted against epidermal growth factor receptor variant III enhances cisplatin efficiency.

Abstract：

PURPOSE:To investigate the effect of a monoclonal antibody (CH12), targeted against epidermal growth factor receptor type III variant (EGFRvIII), on human ovarian cancer cells when administered in combination with cisplatin chemotherapy. METHODS:Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to determine the expression levels of EGFRvIII protein and mRNA, respectively, in the ovarian cancer cell lines SK-OV-3 and CAOV-3. Cells were left untreated or treated with either cisplatin or CH12 alone or both agents in combination (2 μg/ml cisplatin plus CH12). Cell proliferation was detected in a CCK-8 assay. The binding affinities of the CH12 mAb to the 2 cell lines were analyzed; after treatment with cisplatin and different concentrations of CH12, the apoptotic ratios and cell cycle stages of SK-OV-3 cells were determined by flow cytometry (FCM). RESULTS:The express of EGFRvIII mRNA and protein in the two ovarian cancer cell lines were both detected. Analysis of the combination index yielded a value of 0.915, indicating that 2 drugs have a synergistic therapeutic effect. SK-OV-3 cells were observed to be much more resistant to cisplatin than CAOV-3 cells. The primary combinatorial effect of the 2 drugs was the induction of apoptosis, but we also observed synergic co-inhibition of the cell cycle of SK-OV-3 in the S phase. CONCLUSIONS:We conclude that CH12 antibody is a promising candidate for clinical therapy for ovarian cancer cells, which has lower sensitivity to cisplatin treatment; however, the underlying mechanism needs further study.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Li N,Chu Y,Yao L,Ying X,Jiang H,Zhou M,Xu C

doi

10.1007/s00432-011-1018-9

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

1455-61

issue

10

eissn

0171-5216

issn

1432-1335

journal_volume

137

pub_type

杂志文章

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