The mechanisms of 5-FU-PLA-O-CMC-NPS-mediated inhibition of the proliferation of colorectal cancer cell line SW480.

ABSTRACT

We aimed to investigate how 5-FU-PLA-O-CMC-NP (5-FPOCN) inhibits the proliferation of the SW480 colon cancer cell line. Following the treatment of cell line SW480 with 0.1, 1, 10 or 100 µg/ml 5-FPOCN or 5-fluorouracil (fluorouracil, 5-Fu) for 0, 24, 48, or 72, the rate of cell was tested by the tetrazolium assay (MTT). After the SW480 cells were treated with 5-FPOCN or 5-FU for 72 h, the growth rate and apoptosis were detected. After the SW480 cells were treated with 5-FPOCN or 5-FU for 24, 48, 72, or 120, flow cytometry (FCM) was used to determine the cell cycle distribution. The changes in the expression of P21, CyclinD1 and Rb were detected by Western blotting and real-time PCR. We found that different doses of 5-FPOCN can significantly inhibit the growth rate of SW480 cells, and this effect is dose and time dependent. However, there is no significant difference from 72 to 120 h (P>0.05). After 5-FPOCN treatment for 72 h, there is a negative correlation between the concentration of 5-FPOCN and the activity of SW480 cells and a positive correlation between the concentration of 5-FPOCN and SW480 cell apoptosis. G1 phase was significantly increased, and S phase was significantly decreased in 5-FPOCN-treated SW480 cells at 72 h compared to the control group (P<0.05); there was a positive correlation between the concentration of 5-FPOCN and the above changes. It was suggested that 5-FPOCN can delay G1/S phase and that this is a dose-dependent effect. The expression of P21 protein and messenger RNA (mRNA) and Rb protein and mRNA was significantly increased in 5-FPOCN-treated SW480 cells at 72 h compared to the control group, and this was a dose- and time-dependent effect. CyclinD1 protein and mRNA expression was reduced as the dose increased, and its expression was negatively associated with the increased expression of P21. We concluded that 5-FPOCN can significantly inhibit the growth of colon cancer SW480 cells. 5-FPOCN increased P21 expression and decreased cyclin family and pRb expression to promote cell cycle delay and apoptosis.