Molecular regulation of cervical cancer growth and invasion by VEGFa.

Abstract

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.

• Authors: Baohuan Chen, Chunxiao Zhang, Pingping Dong, Yuanying Guo, Nan Mu
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 11 Pg. 11587-93 (Nov 2014) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25135429 (Publication Type: Journal Article)

Chemical References

• RNA, Messenger
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Apoptosis
• Blotting, Western
• Cell Movement
• Cell Proliferation
• Enzyme-Linked Immunosorbent Assay
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• TOR Serine-Threonine Kinases (genetics, metabolism)
• Tumor Cells, Cultured
• Uterine Cervical Neoplasms (genetics, metabolism, pathology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)