[瘦素诱导乳腺癌细胞凋亡抵抗及其机制]

[Apoptosis resistance induced by leptin and its mechanism in breast cancer cells].

作者信息

Zhao Tian-suo, Jiang Hai-ping, Wang Xiu-chao, Ren He, Hao Ji-hui

机构信息

Department of Pancreatic Oncology, Cancer Institute and Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2009 Sep;31(9):651-4.

PMID:20021858

Abstract

OBJECTIVE

To explore the apoptosis resistance induced by Leptin and its mechanism in breast cancer cells in vitro.

METHODS

The leptin-mediated reduction of docetaxel-induced apoptosis in human breast cancer T47D cells was evaluated by TransAM ELISA, MTT and caspase-9 assay. The leptin-promoted survivin expression was analyzed by Western-blot and RT-PCR. The reversing effect of STAT3 knockdown on leptin-induced survivin upregulation was measured by Western-blot and RT-PCR.

RESULTS

Leptin promoted T47D cells proliferation and the inhibitory rate was -63.6%. It reduced docetaxel-induced apoptosis in T47D cells by 31.9%. Leptin at different concentrations promoted survivin protein and mRNA expression in T47D cells. The expression of survivin mRNA was 4.6 fold compared with the T47D cells not treated with leptin(10 nmol/L). The expression of survivin mRNA in T47D cells was 0.55 +/- 0.15 fold after transfected with small interfering RNA (siRNA) of STAT3. The expression of survivin mRNA in STAT3 siRNA group and mock transfected group were 0.56 +/- 0.18 fold and 1.61 +/- 0.22 fold after treated by leptin, respectively. The survivin protein level of T47D mock transfected cells was increased after treated by leptin, but the protein level of T47D transfected with STAT3 siRNA cells were not changed significantly.

CONCLUSION

Leptin/STAT3 signaling is a novel pathway for up-regulation of survivin expression in breast cancer cells.

摘要

目的

探讨瘦素在体外诱导乳腺癌细胞抗凋亡作用及其机制。

方法

通过TransAM ELISA、MTT和caspase-9检测评估瘦素介导的多西他赛诱导人乳腺癌T47D细胞凋亡的减少情况。通过蛋白质免疫印迹法（Western-blot）和逆转录-聚合酶链反应（RT-PCR）分析瘦素促进生存素表达的情况。通过蛋白质免疫印迹法和RT-PCR检测信号转导和转录激活因子3（STAT3）基因敲低对瘦素诱导生存素上调的逆转作用。

结果

瘦素促进T47D细胞增殖，抑制率为-63.6%。它使多西他赛诱导的T47D细胞凋亡减少31.9%。不同浓度的瘦素促进T47D细胞中生存素蛋白和mRNA表达。与未用瘦素（10 nmol/L）处理的T47D细胞相比，生存素mRNA表达增加4.6倍。用STAT3小干扰RNA（siRNA）转染后，T47D细胞中生存素mRNA表达为0.55±0.15倍。瘦素处理后，STAT3 siRNA组和模拟转染组生存素mRNA表达分别为0.56±0.18倍和1.61±0.22倍。瘦素处理后，T47D模拟转染细胞的生存素蛋白水平升高，但转染STAT3 siRNA的T47D细胞蛋白水平无明显变化。