Inhibition of angiogenesis and induction of apoptosis are involved in E1A-mediated bystander effect and tumor suppression

Adenovirus type 5 E1A has been implicated in mediation of tumor suppression . Preclinical gene therapy studies have additionally shown that complete gr owth suppression can be achieved by incomplete transfer of E1A into tumors, suggesting that a bystander effect may also be associated with E1A, In thi s study, we investigated the E1A-mediated bystander effect and the mechanis ms that may be associated with it. By s.c. inoculating nude mice with a mix ture of E1A transfectants and parental cells, we found that the E1A transfe ctants exhibited a bystander effect on inhibition of tumor growth, We furth er showed that E1A mediated suppression of angiogenesis and induction of ap optosis in the tumors, likely contributing to the bystander effect. In addi tion, coculture of E1A transfectants and parental cells in a Transwell unit led to grow-th retardation and apoptosis mediated by the supernatant in th e parental cells, indicating that a secreted factor may also contribute to the bystander effect. Taken together, our results suggested that E1A mediat es a bystander effect on tumor suppression by inhibiting angiogenesis and i nducing apoptosis.