Background and objective: It has been demonstrated that bone morphogenetic protein 7 (BMP7) may both inhibit and enhance cell proliferation of many kinds of cancers, but the impact of BMP7 on lung cancer cells and the exact mechanisms are not clear. The aim of this study is to investigate the effect of BMP7 on proliferation of lung carcinoma cells and explore the roles of different types of I receptors in BMP7 signal transmission by blocking endogenous BMPRIs.
Methods: The levels of expression of BMPIRs (BMP7 type I receptors) mRNA in four different NSCLC (human non-small cell lung tumor) cell lines and HBE (normal human bronchial epithelial) cell were detected by RT-PCR. The responsiveness of pulmonary large carcinoma NCI-H460 cell to BMP7 treatment as well as to a combination of BMP7 and anti-BMPIRs treatment in proliferation were detected by MTT.
Results: RT-PCR showed that NCI-H460 cells expressed all three types of BMPIRs; MTT showed that BMP7 inhibit the proliferation of NCI-H460 cell line. Blocking endogenous BMPR1A, BMPR1B obviously reversed the inhibition of BMP7 on the proliferation of NCI-H460 cell respectively (P = 0.003, P = 0.014). Moreover, blocking both endogenous BMPR1A and BMPR1B almost offset the effect of BMP7 on the proliferation of NCI-H460 cell completely (P < 0.001). But ACVR1A blocking did not affect the proliferation of NCI-H460 cell et al (P = 0.074).
Conclusions: BMP7 signaling via BMPR1A and BMPR1B inhibits the proliferation of pulmonary large carcinoma cell NCI-H460.
背景与目的: 已有的研究发现骨形成蛋白7（bone morphogenetic protein 7, BMP7）具有抑制和促进多种肿瘤发生发展的双重作用，但其对肺癌细胞增殖的影响及其具体机制尚不明确。本实验首先检测了外源性BMP7对肺癌细胞增殖的影响，然后通过在肺癌细胞系中阻断不同的Ⅰ型受体，观察其对BMP7生物学作用的影响，以探讨不同的Ⅰ型受体在BMP7信号传导过程中的作用。
方法: 应用RT-PCR及MTT方法分别检测4种非小细胞肺癌（non-small cell lung cancer, NSCLC）细胞系和人支气管上皮细胞系（HBE）中BMP7 Ⅰ型受体的表达情况及外源性BMP7对肺癌细胞增殖能力的影响，并联合运用抗体阻断的方法阻断NCI-H460细胞中内源性Ⅰ型抗体，采用MTT法检测BMP7对NCI-H460细胞增殖的影响，分析不同的Ⅰ型受体在BMP7信号传导过程中的作用。
结果: NCI-H460细胞系中三种Ⅰ型受体均有表达。外源性BMP7抑制了肺大细胞癌NCI-H460细胞的增殖（P=0.002）。运用特异性抗体阻断NCI-H460细胞内源性BMPR1A、BMPR1B、BMPR1A+BMPR1B后BMP7对NCI-H460增殖的抑制作用明显减弱（P=0.003, P=0.014, P < 0.001），而阻断ACVR1A后BMP7对NCI-H460增殖的抑制作用无明显变化（P=0.074）。
结论: BMP7通过激活BMPR1A、BMPR1B两种Ⅰ型受体抑制NCI-H460细胞的增殖。