The anti-colorectal cancer effect of biphenyl-furocoumarin derivative BFD-6b / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To investigate the inhibitory effect of BFD-6b on colorectal cancer cell growth and its preliminary mechanism. 【Methods】 The inhibitory effect of BFD-6b on the growth of various tumor cells （SW480， MCF-7， T47D， SMMC-7721， BEL-7402， 97H， SK-HEP-1， H460， H1299， A549， MS751， and HELA） was investigated by MTT assay； the effect of BFD-6b on apoptosis and cell cycle was detected by flow cytometry； the effect of BFD-6b on the expressions of cell cycle-related proteins and apoptosis-related proteins was examined by Western blotting. 【Results】 BFD-6b inhibited the proliferation of different cancer cells such as SW480， MCF-7， H460， H1299， A549， and HELA. Among all of them， SW480 cells were most sensitive to BFD-6b， and the IC50 value was 7.09 μmol/L. Furthermore， BFD-6b could inhibit the growth of another three colorectal cell （SW620， Lovo， and HCT116 cells）； the IC50 values were 7.23， 8.08 and 8.96 μmol/L， respectively. BFD-6b could downregulate the amount of cyclinD1， cyclinE， and cell cycle-dependent kinase CDC2， thereby arresting the cell cycle at G1 phase. Also， BFD-6b downregulated the expressions of anti-apoptotic proteins Mcl-1 and Bcl-2， and upregulated the expressions of pro-apoptotic proteins BAK and BAX， thus inducing apoptosis of SW480 cells. 【Conclusion】 BFD-6b arrests SW480 cells at G1 phase by downregulating the expressions of cyclinD1， cyclinE and CDC2， and induces SW480 cell apoptosis by downregulating the expressions of Mcl-1 and Bcl-2 and upregulating the expressions of BAK and BAX， thereby inhibiting the proliferation of colorectal cancer SW480 cells.