[Effects of single versus combined use of trastuzumab and cantide on breast cancer cells SKBR3 over-expressing HER2].

ABSTRACT

OBJECTIVE: To evaluate the in vitro cytotoxic effects of cantide or herceptin on human breast cancer SKBR3 cells over-expressing HER2. METHODS: The distribution of HER2 and hTERT protein in SKBR3 cells and the effects of cantide and/or herceptin on the subcellular localization of HER2 and hTERT were observed by indirect immunofluorescent assay. The inhibition rate of herceptin and/or cantide at different concentrations on SKBR3 cells was detected by MTT assay. And the apoptotic rate of cells was evaluated by flow cytometer. RESULTS: (1) The expressions of both HER2 and hTERT proteins in SKBR3 cells were found. HER2 protein was predominant in cell membranes while hTERT protein in nuclei. After the addition of herceptin, the cytoplasmic migration of HER2 was found while there was no distinct location change of cantide. (2) In MTT assay, the single use of cantide or herceptin and the combined use of both produced inhibitory effects on SKBR3 cells while the inhibition rate was higher for combined use. The inhibitory effects became additive in the combined use of 0.4 µmol/L cantide and 0.85 µg/ml herceptin. And there were synergistic effects in the combined use of 0.4 µmol/L cantide and 1.70, 3.40, 6.88 or 13.75 µg/ml herceptin. (3) The apoptotic rate was 25.75% for cantide alone, 11.26% for herceptin alone and 41.41% for their combined use (apoptotic cells predominant in advanced stage). CONCLUSION: Due to different localizations, cantide and herceptin have different action sites in their combined use. When in single use, the inhibition rate is linearly correlated with the concentration of herceptin or cantide. And their combined use produces additive or synergistic antitumor effects on SKBR3 breast cancer cells.