Anticancer effect of rapamycin on MCF-7 via downregulation of VEGF expression.

Abstract

The importance of mTOR signaling in tumor biology is widely accepted and a number of agents that selectively target mTOR are being developed in cancer therapy. On the other hand, it has been demonstrated that mTOR can act as an angiogenic agent. Thus, we hypothesized that the mTOR inhibitor-induced anticancer effect is affected by expression of a key angiogenic factor, vascular endothelial growth factor (VEGF) and investigated the anticancer effect underlying mTOR using an in vitro assay. The mTOR inhibitor rapamycin dose-dependently reduced the cell viability of the breast cancer cell line, MCF-7, but did not reduce the cell viability of the colon cancer cell line, HT-29. Rapamycin reduced the VEGF expression in the culture medium of MCF-7, while rapamycin did not contribute VEGF expression in the culture medium of HT-29. VEGF stimulated cell viability and VEGF inhibition reduced cell viability of MCF-7, and rapamycin dose-dependently restored the cell viability of MCF-7 reduced by rapamycin. These findings suggest that mTOR acts as a direct anticancer agent and that the mTOR-inhibitor-induced anticancer effect involved the reduced expression of VEGF in MCF-7. Our results imply that mTOR regulates the expression of VEGF and is involved in breast cancer progression.

• Authors: Takaaki Fujii, Reina Yajima, Hironori Tatsuki, Katuya Oosone, Hiroyuki Kuwano
• Journal: In vitro cellular & developmental biology. Animal (In Vitro Cell Dev Biol Anim) Vol. 52 Issue 1 Pg. 45-8 (Jan 2016) ISSN: 1543-706X [Electronic] Germany
• PMID: 26427711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Kinase Inhibitors
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• MTOR protein, human
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Breast Neoplasms (drug therapy, genetics, pathology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MCF-7 Cells
• Protein Kinase Inhibitors (administration & dosage)
• Sirolimus (administration & dosage)
• TOR Serine-Threonine Kinases (antagonists & inhibitors, genetics)
• Vascular Endothelial Growth Factor A (biosynthesis, genetics)