Molecular regulation of cervical cancer growth and invasion by VEGFa
Molecular regulation of cervical cancer growth and invasion by VEGFa
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DOI：
10.1007/s13277-014-2463-2
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发表时间：
2014-11-01
期刊：
影响因子：
--
通讯作者：
Mu, Nan
中科院分区：
文献类型：
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作者：
Chen, Baohuan;Zhang, Chunxiao;Mu, Nan
尽管抗血管内皮生长因子a（VEGFa）治疗已在宫颈癌治疗中得到很好的应用，但其潜在的分子基础尚未被精确确定。在这里，我们检测了 VEGFa 水平对四种常用人宫颈癌细胞系肿瘤生长和侵袭的影响。我们发现这些细胞系中 VEGFa 的过度表达增加了肿瘤的生长和侵袭性，而抑制 VEGFa 则降低了肿瘤的生长和侵袭性。为了弄清楚所涉及的信号通路，我们分别将 ERK/MAPK、JNK 和 PI3K/Akt 信号通路的特异性抑制剂应用于 VEGFa 过表达的宫颈癌细胞系，发现只有抑制 PI3K/Akt 信号转导才能消除 VEGFa 诱导的细胞生长和侵袭性增加。抑制 Akt 下游 mTor 信号通路同样会抑制 VEGFa 过表达的宫颈癌细胞的细胞生长和侵袭，这表明 VEGFa 可能激活 PI3K/Akt 及其下游 mTor 信号通路，从而促进宫颈癌细胞生长和侵袭。此外，VEGFa 诱导的 mTor 信号级联激活似乎可以通过 cyclinD1 和 CDK4 激活促进癌细胞生长，并通过 MMP2 和 MMP3 促进癌细胞侵袭。综上所述，我们的数据表明，宫颈癌的抗 VEGFa 治疗可能通过 PI3k/Akt/mTor 信号通路抑制肿瘤细胞的生长和侵袭。
Although antivascular endothelial growth factor a (VEGFa) treatment has been well applied in cervical cancer therapy, the underlying molecular basis has not been precisely identified. Here, we examined the levels of VEGFa on the tumor growth and invasion in four commonly used human cervical cancer cell lines. We found that overexpression of VEGFa in these lines increased the tumor growth and invasiveness, while inhibition of VEGFa decreased the tumor growth and invasiveness. To figure out the involved signaling pathways, we applied specific inhibitors for ERK/MAPK, JNK, and PI3K/Akt signaling pathways, respectively, to VEGFa-overexpressing cervical cancer lines and found that only inhibition of PI3K/Akt signal transduction abolished VEGFa-induced increases in cell growth and invasiveness. Inhibition of Akt downstream mTor signaling similarly inhibited cell growth and invasion in VEGFa-overexpressing cervical cancer cells, suggesting that VEGFa may activate PI3K/Akt, and subsequently its downstream mTor signaling pathway, to promote cervical cancer cell growth and invasion. Furthermore, the effects of VEGFa-induced activation of mTor signaling cascades appeared to promote cancer cell growth through cyclinD1 and CDK4 activation and promote cancer cell invasion through MMP2 and MMP3. Taken together, our data suggest that anti-VEGFa treatment in cervical cancer may inhibit both tumor cell growth and invasion through PI3k/Akt/mTor signaling pathway.