镧和钆对DU145细胞诱导的前成骨细胞和破骨细胞分化的影响

The influence of La and Gd on prostate cancer DU145 cell-induced osteoblast and osteoclast differentiation

为探索稀土化合物在防治前列腺癌骨转移方面的潜在药理作用,研究了镧(La)和钆(Gd)对前列腺癌细胞DU145诱导的成、破骨细胞分化的影响.实验结果表明,DU145细胞的条件培养基能够促进小鼠前成骨细胞MC3T3-e1的增殖、ALP活性和钙沉积,而且经La处理后作用进一步加强.然而Gd处理后的DU145细胞条件培养基组对MC3T3-e1的ALP活性和钙沉积影响并不显著.RT-PCR实验表明,La可能通过上调DU145细胞分泌的细胞因子BMP6表达,抑制Noggin的表达进而促进成骨细胞的增殖和分化;而且成骨细胞的增殖、分化与JNK信号转导通路有关.此外,还观察到La能够抑制DU145细胞诱导的破骨细胞生成,并且通过下调前列腺癌细胞RANKL的表达而起到抑制作用.然而Gd对DU145细胞诱导的破骨细胞生成的影响并不显著.

To assess the potential effect of lanthanides （Ln） on the prevention of prostate cancer （PCa） bone metastasis, in this study we report the influence of Ln on PCa cells induced osteoblasts and osteoclasts differentiation. We cultured osteoblast-like MC3T3-el cells with conditioned medium （CM） from lanthanum （La）or gadolinium （Gd） treated DU145 cells. MC3T3-el differentiation increased in the presence of DU145 CM treated with La, whereas Gd treatment hadno effect on MC3T3-el differentiation. Using RT-PCR arrays, we observed an increase in the expression of BMP6 genes in DU145 cells treated with La. Western blot analysis demonstrated that LaC13 treatment increased phosphorylation of c-Jun NH（2）-terminal kinase （JNK）. In addition, La reduced the expression of osteoclastogenesis-associated genes RANKL while increasing OPG expression in DU145 cells. Furthermore, La inhibited DU145 cells induced osteoclast formation in an in vitro coculture model of prostate cancer cells with osteoclast precursors generated from mouse bone marrow cells, while Gd failed to show the similar phenomenon in osteoclast differentiation.