Inhibition of melanoma tumor growth in vivo by survivin targeting

A role of apoptosis (programmed cell death) in tumor formation and growth w as investigated by targeting the apoptosis inhibitor survivin in vivo. Expr ession of a phosphorylation-defective survivin mutant (Thr(34)-->Ala) trigg ered apoptosis in several human melanoma cell lines and enhanced cell death induced by the chemotherapeutic drug cisplatin in vitro. Conditional expre ssion of survivin Thr(34)-->Ala in YUSAC2 melanoma cells prevented tumor fo rmation upon s.c. injection into CB.17 severe combined immunodeficient-beig e mice. When induced in established melanoma tumors, survivin Thr(34)-->Ala inhibited tumor growth by 60-70% and caused increased apoptosis and reduce d proliferation of melanoma cells in vivo. Manipulation of the antiapoptoti c pathway maintained by survivin may be beneficial for cancer therapy.