In this study, we addressed antiproliferative effects of trastuzumab (Herceptin®) and nimotuzumab (Theraloc®) in a combined application with EGF on MCF-7 cells. The epidermal growth factor (EGF) receptors have been found to be implicated in the ontology and maintenance of tumor tissues, which has fostered the discovery and development of molecularly targeted anti-EGF-receptor therapies. However, the accessibility of chemotherapeutic preparations and humanized antibodies to tumor cells in the G0 phase of the cell cycle is lower than to the cells of theproliferative pool. Given this, antitumor efficiency can potentially be enhanced by synchronizing cells in the proliferative pool. To explore this opportunity, we added EGF to tumor cells in combination with nimotuzumab and trastuzumab (antibodies against EGF-R typeI and II, respectively).
We added aforementioned compounds to MCF-7 cells in the exponential and stationary phases of growth. Cytotoxic/cytostatic effects and cell survival were assessed by the MTT assay, cytofluorimetry and counting cells stained with trypan blue.
The cytotoxic/cytostatic effect of nimotuzumab in combination with EGF was 56% relative to control, whereas nimotuzumab alone resulted in 45%. In the stationary phase of growth, application of nimotuzumab+EGF did not reveal any effects. Trastuzumab did not produce any antiproliferative effects in combination with EGF during exponential growth, but this combination led to a 60% cytotoxic/cytostatic effect in the stationary phase. Application of trastuzumab alone resulted in a 17% effect during exponential growth and 23% in the stationary phase of MCF-7 cells growth. Trastuzumab in combination with EGF can inhibit cell migratory activity. This combination leads to twice decreased migration area for 2 D growth mode, and 20% for spheroid mode. Trastuzumab also promotes cells attachment to substrate under the serum starvation conditions. Index of adhesion increases in 1,5 times. The combination of trastuzumab and EGF usage promote twice increased adhesion. Nimotuzumab in combination with EGF doesn’t demonstrate any detectible influence on MCF-7 cells adhesion or migration. All the data were statistically significant at p < 0.05.
Utilization humanized antibodies against the EGF receptor in complex with EGF may be considered as a potentially efficient antitumor combination.
Taras Shevchenko National University of Kyiv
Has not received any funding
All authors have declared no conflicts of interest.