Blockage of TGF-α Inducing by Spherical Silica Nanoparticles Inhibits Epithelial-Mesenchymal Transition and Proliferation of Human Lung Epithelial Cells
Blockage of TGF-α Inducing by Spherical Silica Nanoparticles Inhibits Epithelial-Mesenchymal Transition and Proliferation of Human Lung Epithelial Cells
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球形二氧化硅纳米粒子诱导的 TGF-α 阻断抑制人肺上皮细胞的上皮-间质转化和增殖
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通讯作者：
ZiJie Liu
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作者：
YiXun Li;Huan Li;Yong Duan;XueMei Cai;DingYun You;Feng zhou;ChuanQi Yang;XiaoYu Tuo;ZiJie Liu
背景资料。云南省宣威市一直是中国肺癌死亡率最高的乡镇之一。云南宣威烟煤中无定形二氧化硅含量较高，主要以不规则球形二氧化硅纳米颗粒(SiNPs)的形式存在。有报道称，烟煤中的二氧化硅纳米颗粒与宣威肺癌的高发有关。为探讨SiNPs在宣威肺癌发生中的作用及机制，将人单核细胞(THP-1)与人支气管上皮细胞(BEAS-2B)在Transwell小室中共培养。SiNPs与苯并[a]芘-7，8-二氢二醇-9，10-环氧化物联合使用可显著促进BEAS-2B细胞的增殖和上皮-间充质转化，抑制细胞凋亡，并诱导THP-1细胞释放转化生长因子-α。用抗体中和转化生长因子-α后，BEAS-2B细胞的增殖和转移率降低，细胞凋亡率增加。结果表明，宣威肺腺癌患者血清转化生长因子-α水平显著高于宣威肺良性病变患者和云南宣威外肺腺癌患者。综上所述，我们的研究发现，SiNPs通过诱导THP-1细胞释放转化生长因子-α来促进BEAS-2B细胞的增殖和EMT。
Background. Xuanwei City in Yunnan province has been one of the towns with highest lung cancer mortality in China. The high content of amorphous silica in the bituminous coal from Xuanwei of Yunnan is mainly present as irregular and spherical silica nanoparticles (SiNPs). It has been reported that silica nanoparticles in bituminous coal correlated with the high incidence of lung cancer in Xuanwei. To explore the role and mechanism of SiNPs in the tumorigenesis of lung cancer in Xuanwei, human mononuclear cells (THP-1) and human bronchial epithelial cells (BEAS-2B) were co-cultured in a transwell chamber. Combined with Benzo[a]pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE), SiNPs could significantly promote the proliferation and Epithelial-Mesenchymal Transition (EMT) and inhibit apoptosis of BEAS-2B cells, and induce the release of TGF-α from THP-1 cells. After neutralizing TGF-α with antibody, the proliferation and EMT were decreased and enhanced apoptosis of BEAS-2B cells. Furthermore, the results showed that TGF-α in the sera of patients with lung adenocarcinoma in Xuanwei were significantly higher than in patients with benign pulmonary lesions in Xuanwei and those with lung adenocarcinoma in outside of Xuanwei of Yunnan. Taken together, our study found that SiNPs promoted the proliferation and EMT of BEAS-2B cells by inducing the release of TGF-α from THP-1 cells.