Gemcitabine, which induces S-phase arrest, and Vinorelbine, which arrests microtubule
organization, are two agents that have demonstrate preferred anti-tumor activity.
Nitric oxide acts in diverse functions including anti-tumor and anti-pathogenic activities.
In this study, we aimed to examine the distribution of immunoreactivities of inducible
nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in cells
of the MCF-7 breast cancer cell line in response to treatment with Gemcitabine (G),
Vinorelbine (V) and combination of Gemcitabine and Vinorelbine (G+V). The distributions
of iNOS and eNOS were determined by using indirect immunoperoxidase or immunofluorescence
methods and ELISA. Cells incubated with G, V and G+V for 24, 48 and 72h were immunolabelled
with anti-eNOS and anti-iNOS primary antibodies. Apoptosis was determined by TUNEL
assay. A significant increase of eNOS immunolabelling on MCF-7 cells treated with
G and G+V was observed. Apoptotic cells were also detected in G, V and G+V treated
MCF-7 cells. The immunolabelling of iNOS was detected in all groups but this immunoreactivity
was not different among the groups. In conclusion, while G treatment, induced S-phase
arrest, triggered the NOS pathway after treatment of MCF-7 cells, V treatment, arrested
microtubule organization and did not change the NOS pathway. Detection of increased
eNOS immunolabelling and apoptosis after G treatment of MCF-7 cells could be important
to the treatment of human breast cancer.