title: MK886 inhibits the pioglitazone-induced anti-invasion of MDA-MB-231 cells is associated with PPARα/γ, FGF4 and 5LOX.
abstract: The goal of this study was to determine the effects of PGZ and MK886 on the mRNA expression of PPARα and other associated genes in MDA-MB-231 cells, and the biological mechanisms induced by both drugs were also assessed. The levels of PPARα mRNA expression in PGZ-treated and MK886-treated MDA-MB-231 cells were determined using real-time PCR; the growth inhibitory effects of PGZ and MK886 were determined using the trypan blue exclusion assay; the induction of apoptosis by PGZ and MK886 was determined using DNA fragmentation assay and real-time PCR; and the invasion of PGZ-treated and MK886-treated MDA-MB-231 cells was determined using the wound healing and transwell migration assays. In addition, we correlated the expression of PPARα mRNA with other genes, including PPARγ, FGF4 and 5LOX, in drug-treated MDA-MB-231 cells. Our results demonstrated that the treatment of MDA-MB-231 cells with PGZ increased the expression of PPARα/γ mRNA and that this expression could be inhibited by treatment with MK886. Both drugs reduced the viability of MDA-MB-231 cells independently of PPARα/γ mRNA expression but did not induce apoptosis. The wound caused by invasion was not healed by PGZ-treated MDA-MB-231 cells, but it was healed by MK886-treated cancer cells, indicating that the reduction of invasion in PGZ-treated MDA-MB-231 cells was eliminated by treatment with MK886, and this finding was validated by the transwell migration assay. This phenomenon might also be associated with the expression of PPARα/γ, FGF4 and 5LOX mRNA in the treated cancer cells. This study provides useful information regarding the mRNA expression levels of PPARα and other related genes in MDA-MB-231 cells. These genes could be attractive targets for reducing the invasion of breast cancer.
authors.affiliation: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.
authors.forename: Kalpanah
authors.initials: K
authors.lastname: Nadarajan
authors.affiliation: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.
authors.forename: Prabha
authors.initials: P
authors.lastname: Balaram
authors.affiliation: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia. kboonyin@yahoo.com.
authors.forename: Boon Yin
authors.initials: BY
authors.lastname: Khoo
keywords: Cell invasion; MDA-MB-231; MK886; PPARα; Pioglitazone