骨形成蛋白7通过激活Ⅰ型受体BMPR1A、BMPR1B抑制肺大细胞癌NCI-H460细胞的增殖

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). CONCLUSION: BMP7 signaling via BMPR1A and BMPR1B inhibits the proliferation of pulmonary large carcinoma cell NCI-H460.