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

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.