ABSTRACT
Objective To explore effects of paclitaxel on proliferation and migration of breast cancer Michigan Cancer Foundation-7 (MCF-7) cells via mammalian target of rapamycin (mTOR) signaling pathway.Methods The cases were randomly divided into four groups,including control group,paclitaxel low-dose group (0.25 μmol/L),paclitaxel medium-dose group (0.5 μmol/L),and paclitaxel high-dose group (1 μmol/L).The viability of MCF-7 cells was measured with methyl thiazolyl tetrazolium (MTT) assay.MCF-7 cell cycle was examined with flow cytometry.MCF-7 cell migration was tested with transwell migration assay.The levels of mTOR signalling pathway-related protein were assayed with Western blot.Results Compared to the control group,MCF-7 cell viability was significantly decreased in paclitaxel low,medium and high-dose groups (P ＜ 0.05),and the inhibitory rate was highest at 48 h (P ＜ 0.05).MCF-7 cell migration was significantly inhibited in paclitaxel low,medium and high-dose groups [(98 ± 9.78) vs (86.21 ± 6.58),(53.41 ± 3.16) and (42.00 ± 4.69),P ＜ 0.05].Moreover,compared to the control group,the number of MCF-7 cells at G1 phase was significantly increased in paclitaxel low,medium and high-dose groups [(52.14±6.13)％ vs (67.93 ±8.16)％,(72.32 ±3.67)％ and (78.53 ± 6.28)％,P ＜ 0.01],the number of MCF-7 cells at G2 phase was significantly reduced in paclitaxel low,medium and high-dose group [(13.68 ± 0.85) ％ vs (8.57 ± 1.03) ％,(5.30 ± 0.89) ％ and (3.46 ± 0.78) ％,P ＜0.01].The phosphorylations of 4E binding protein (4EBP1) and mTOR proteins as well as the expressions of cell-cycle protein D1 (Cyclin D1) and matrix metalloproteinase-9 (MMP-9) were significantly inhibited in paclitaxel low,medium and high-dose groups (P ＜ 0.01).Conclusions These results suggested paclitaxel could inhibit proliferation and migration in breast cancer MCF-7 cells,which might be related to mTOR signal pathway.
ABSTRACT
The overexpression of P-glycoprotein(P-gp)and its coding gene mdrl is regarded as the classic mechanism of muhidrug resistance(MDR).Recent studies find that pregnane X receptor(PXR)can mediate the expression of P-gp.It is confirmed that PXR can also inhibit apoptosis of tumor cells.Therefore,preventing the activation of PXR specifically may be a new method to prevent MDR.