TCTP作为黑色素瘤治疗的一个治疗靶点。
TCTP as a therapeutic target in melanoma treatment.
作者信息
Boia-Ferreira M, Basílio A B, Hamasaki A E, Matsubara F H, Appel M H, Da Costa C R V, Amson R, Telerman A, Chaim O M, Veiga S S, Senff-Ribeiro A
机构信息
Department of Cell Biology, Centro Politécnico, Federal University of Paraná, UFPR, Jardim das Américas, CEP 81531-990, Curitiba, Paraná, Brazil.
Department of Structural, Molecular Biology and Genetics, State University of Ponta Grossa, Ponta Grossa, Paraná, Brazil.
出版信息
Br J Cancer. 2017 Aug 22;117(5):656-665. doi: 10.1038/bjc.2017.230. Epub 2017 Jul 27.
BACKGROUND
Translationally controlled tumour protein (TCTP) is an antiapoptotic protein highly conserved through phylogeny. Translationally controlled tumour protein overexpression was detected in several tumour types. Silencing TCTP was shown to induce tumour reversion. There is a reciprocal repression between TCTP and P53. Sertraline interacts with TCTP and decreases its cellular levels.
METHODS
We evaluate the role of TCTP in melanoma using sertraline and siRNA. Cell viability, migration, and clonogenicity were assessed in human and murine melanoma cells in vitro. Sertraline was evaluated in a murine melanoma model and was compared with dacarbazine, a major chemotherapeutic agent used in melanoma treatment.
RESULTS
Inhibition of TCTP levels decreases melanoma cell viability, migration, clonogenicity, and in vivo tumour growth. Human melanoma cells treated with sertraline show diminished migration properties and capacity to form colonies. Sertraline was effective in inhibiting tumour growth in a murine melanoma model; its effect was stronger when compared with dacarbazine.
CONCLUSIONS
Altogether, these results indicate that sertraline could be effective against melanoma and TCTP can be a target for melanoma therapy.
背景
翻译调控肿瘤蛋白（TCTP）是一种在系统发育过程中高度保守的抗凋亡蛋白。在多种肿瘤类型中均检测到翻译调控肿瘤蛋白的过表达。沉默TCTP可诱导肿瘤逆转。TCTP与P53之间存在相互抑制作用。舍曲林与TCTP相互作用并降低其细胞水平。
方法
我们使用舍曲林和小干扰RNA（siRNA）评估TCTP在黑色素瘤中的作用。在体外对人源和鼠源黑色素瘤细胞的细胞活力、迁移能力和克隆形成能力进行评估。在鼠源黑色素瘤模型中评估舍曲林，并与黑色素瘤治疗中使用的主要化疗药物达卡巴嗪进行比较。
结果
抑制TCTP水平可降低黑色素瘤细胞的活力、迁移能力、克隆形成能力以及体内肿瘤生长。用舍曲林处理的人源黑色素瘤细胞显示出迁移特性和形成集落能力减弱。舍曲林在鼠源黑色素瘤模型中有效抑制肿瘤生长；与达卡巴嗪相比，其效果更强。
结论
总之，这些结果表明舍曲林可能对黑色素瘤有效，且TCTP可成为黑色素瘤治疗的靶点。
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