LDN-193189对人去分化软骨肉瘤细胞系NDCS-1的抑制作用研究*

2016-03-31杨康汤小东郭卫

中国肿瘤临床 2016年2期

关键词：实验

杨康　汤小东　郭卫

LDN-193189对人去分化软骨肉瘤细胞系NDCS-1的抑制作用研究*

杨康汤小东郭卫

摘要目的：检测骨形成蛋白（BMP）受体抑制剂LDN-193189对人去分化软骨肉瘤（DDCS）细胞系NDCS-1的抑制作用，探讨LDN-193189对去分化软骨肉瘤的抑癌机制。方法：以5 nmol/L的LDN-193189作用于NDCS-1细胞，MTT、平板克隆法检测LDN-193189对NDCS-1细胞的增殖抑制作用，Transwell法、划痕实验检测LDN-193189对NDCS-1细胞的侵袭抑制作用，Western blot检测BMPR2、p-Smad1/5及RUNX2的蛋白表达抑制情况。结果：药物处理后NDCS-1细胞增殖、侵袭被明显抑制；药物处理后NDCS-1细胞的BMPR2、p-Smad1/5及RUNX2蛋白表达下降。结论：LDN-193189通过抑制BMPR2-p-Smad1/5-RUNX2信号传导通路能有效抑制去分化软骨肉瘤细胞系NDCS-1的增殖侵袭能力。

关键词去分化软骨肉瘤LDN-193189 NDCS-1 BMPR2 p-Smad1/5 RUNX2

*本文课题受国家自然科学基金项目（编号：81172544）和教育部新世纪人才项目（编号：NCET-12-0007）资助

LDN-193189inhibits progression and induces apoptosis in human dedifferentiated chondrosarcoma cell line NDCS-1

Kang YANG, Xiaodong TANG, Wei GUO
Correspondence to: Xiaodong TANG; E-mail: tang15877@126.com
Department of Bone Oncology, Peking University, People's Hospital, Beijing 100044, China
This work was supported by the Natural Science Foundation of China（No.81172544）and the Program for New Century Excellent Talents in University（No.NCET-12-0007）

Abstract Objective: To clarify the effects of the BMP receptor inhibitor LDN-193189 in the dedifferentiated chondrosarcoma（DDCS）cell line NDCS-1 and to explore the anti-tumor mechanismof LDN-193189 in DDCS.Methods: NDCS-1 was treated with 5 nmol/L of LDN-193189.MTT assay and clone formation experiments were used to verify that LDN-193189 suppressed cell proliferation.Transwell and wound healing tests were performed to demonstrate that LDN-193189 inhibited cell invasion.Western blot detection was used to show that LDN-193189 inhibited the suppression of BMPR2, p-Smad1/5, and RUNX2 protein expression.Results: The BMPR2 signaling pathway was inhibited by LDN-193189; thus, cell viability and invasion were significantly suppressed.Conclusion: LDN-193189 induces the inhibition of progression in vitro via the BMPR2-p-Smad1/5-RUNX2 signaling pathway in the human DDCS cell line NDCS-1.

Keywords:dedifferentiated chondrosarcoma, LDN-193189, NDCS-1, BMPR2, p-Smad1/5, RUNX2

去分化软骨肉瘤是一种特殊的软骨肉瘤，约占所有软骨肉瘤的10%［1］，软骨肉瘤一旦发生去分化改变，肿瘤侵袭性明显增高［2］。由于早期转移与放化疗不敏感，去分化软骨肉瘤预后极差，5年生存率为10%～24%［3-5］。以往实验室研究表明去分化软骨肉瘤中BMPR2、RUNX2表达明显高于普通软骨肉瘤［6-7］，抑制BMPR2能够控制肿瘤的发生发展［8］，而LDN-193189是BMP受体特异性抑制剂，因此本研究以去分化软骨肉瘤细胞系NDCS-1为研究对象，观察LDN-193189对NDCS-1细胞的作用并检测BMPR2及下游基因p-Smad1/5、RUNX2的表达，探讨LDN-193189对NDCS-1细胞的作用机制，为后续体内实验与临床应用提供前期研究基础。