Experimental Research On Treatment Of Breast Cancer With Recombinant EGFR Antisense Adenovirus Plus Ionizing Radiation

Background: Epidermal growth factor receptor or HER-1/erbB-1 is a member of the trans-membrane receptor with tyrosine kinase activity, HER/erbB family, which plays important roles in regulating tumor proliferation, metastasis, invasion and DNA reparation. EGFR expresses in all of the normal epidermal cells, its over-expression, gene amplification and mutation are detected in many tumors. In an experimental model, we found that EGFR expression augmented with tumorigenicity increase, and the transformed phenotype could be reversed after transfection with an EGFR antisense RNA expressing vector. In order to find a new therapeutic manner for breast cancer, we exploited a recombinant EGFR antisense adenovirus, AdE5, and find it can increase the anti-tumor effect of ionizing radiation on breast cancer cells in vitro.Objective: To investigate the antitumor effects of recombinant EGFR antisense adenovirus (AdE5) plus radiation on breast cancer cells.Methods: Human EGFR cDNA fragment was subcloned in the opposite orientation to the cytomegaloviral promoter and inserted into an E1/E3-deleted type 5 adenoviral vector to obtain AdE5 construct which expresses EGFR antisense RNA. MDA-MB-231 human breast cancer cells were cultured in vitro and then injected s.c. into right flanks of nude mice. Two intra-tumoral injections of 100 μl PBS buffer containing 10~9pfu of AdE5 or AdCO1 or PBS alone were practiced every other day, tumors were then irradiated 6Gy once using 6 MeV electronic ray. Effects of AdE5 on tumor growth, Ki-67 expression and MVD were evaluated.Results: AdE5 inhibited tumor growth, and the tumor relative growth index was decreased more severely when it was combined with ionizing radiation ascompared with other control groups (p<0.01). Immunohistochemical study showed that intra-tumoral Ki-67 expression and MVD were significantly inhibited by AdE5 plus ionizing radiation, when compared with other control groups (p<0.01)Conclusion: Recombinant EGFR antisense adenovirus is effective for inhibition of breast cancer cell growth in vivo, and for increase of the anti-tumor effect of ionizing radiation in this breast cancer model.