Inhibition of melanoma tumor growth in vivo by survivin targeting.
Inhibition of melanoma tumor growth in vivo by survivin targeting.
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DOI：
10.1073/pnas.98.2.635
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发表时间：
2001-01
影响因子：
11.1
通讯作者：
D. Grossman;P. J. Kim;J. Schechner;D. Altieri
中科院分区：
文献类型：
--
作者：
D. Grossman;P. J. Kim;J. Schechner;D. Altieri
通过体内靶向凋亡抑制因子Survivin，研究了细胞凋亡(程序性细胞死亡)在肿瘤形成和生长中的作用。表达磷酸化缺陷的Survivin突变体(Thr(34)--&Gt；Ala)可在体外诱导几种人黑色素瘤细胞系的凋亡，并增强化疗药物顺铂诱导的细胞死亡。Survivin Thr(34)-->；Ala在YUSAC2黑色素瘤细胞中的条件性表达可阻止S.C.CB.17重度联合免疫缺陷-褐变小鼠。当在已建立的黑色素瘤中诱导时，Survivin Thr(34)-->；Ala在体内抑制肿瘤生长60%-70%，并导致黑色素瘤细胞凋亡增加和增殖减少。操纵Survivin维持的抗凋亡通路可能有利于癌症的治疗。
A role of apoptosis (programmed cell death) in tumor formation and growth was investigated by targeting the apoptosis inhibitor survivin in vivo. Expression of a phosphorylation-defective survivin mutant (Thr(34)-->Ala) triggered apoptosis in several human melanoma cell lines and enhanced cell death induced by the chemotherapeutic drug cisplatin in vitro. Conditional expression of survivin Thr(34)-->Ala in YUSAC2 melanoma cells prevented tumor formation upon s.c. injection into CB.17 severe combined immunodeficient-beige mice. When induced in established melanoma tumors, survivin Thr(34)-->Ala inhibited tumor growth by 60-70% and caused increased apoptosis and reduced proliferation of melanoma cells in vivo. Manipulation of the antiapoptotic pathway maintained by survivin may be beneficial for cancer therapy.