下调 TGF-β1 通过促进 BRCA1/Smad3 信号通路抑制卵巢癌细胞增殖并增加其化疗敏感性。
Downregulation of TGF-β1 suppressed proliferation and increased chemosensitivity of ovarian cancer cells by promoting BRCA1/Smad3 signaling.
机构信息
Reproductive Medical Center, Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
出版信息
Biol Res. 2018 Dec 29;51(1):58. doi: 10.1186/s40659-018-0205-4.
BACKGROUND
Studies have demonstrated that transforming growth factor beta-1 (TGF-β1) exhibits oncogenic activity in different types of cancer, including ovarian cancer (OC). However, its regulatory mechanism in OC and whether TGF-β1 is involved in chemosensitivity regulation remains unclear. Thus, the aim of this study was to investigate the role of TGF-β1 in OC.
METHODS
The OC cell line SKOV3 was employed, and TGF-β1 overexpression or knockdown vectors were constructed. The cell proliferation of SKOV3 was evaluated with the cell counting kit (CCK8) kit after treatment with different concentrations of cis-platinum. Western blot and protein immunoprecipitation were employed to detect changes in BRCA1 and Smad3 expression and their interactions. Tumor growth in nude mice was evaluated.
RESULTS
The results showed that TGF-β1 knockdown increased chemosensitivity by promoting BRCA1 expression and Smad3 phosphorylation. In vivo studies showed that TGF-β1 knockdown significantly inhibited the growth of tumors, also by upregulating BRCA1 expression and Smad3 phosphorylation.
CONCLUSION
Taken together, our results suggest that TGF-β1 knockdown inhibits tumor growth and increases chemosensitivity by promotion of BRCA1/Smad3 signaling.
背景
研究表明转化生长因子-β1（TGF-β1）在多种癌症中具有致癌活性，包括卵巢癌（OC）。然而，其在 OC 中的调控机制以及 TGF-β1 是否参与化疗敏感性调节尚不清楚。因此，本研究旨在探讨 TGF-β1 在 OC 中的作用。
方法
采用 OC 细胞系 SKOV3，构建 TGF-β1 过表达或敲低载体。用不同浓度顺铂处理后，用细胞计数试剂盒（CCK8）检测 SKOV3 细胞的增殖情况。采用 Western blot 和蛋白质免疫沉淀检测 BRCA1 和 Smad3 表达及其相互作用的变化。评估裸鼠肿瘤生长情况。
结果
结果表明，TGF-β1 敲低通过促进 BRCA1 表达和 Smad3 磷酸化增加化疗敏感性。体内研究表明，TGF-β1 敲低通过上调 BRCA1 表达和 Smad3 磷酸化显著抑制肿瘤生长。
结论
综上所述，我们的研究结果表明，TGF-β1 敲低通过促进 BRCA1/Smad3 信号通路抑制肿瘤生长并增加化疗敏感性。
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