Study Of Antitumor Effect Of Curcumin Derivative C1204in Vitro And In Vivo

OBJECTIVE To study the antitumor effect of curcumin derivative C1204in vitroand in vivo.METHODS1. The MTT assay and was used for detection the activity of proliferation inhibition ofC1204on K562、K562/G01、HT-29、CNE2、SGC7901、SW620、SMMC7721tumor cell lines.2. The colony-forming assay was applied for determining the forming of colonies ofK562、K562/G01、HT-29、CNE2、SGC7901、SW620、SMMC7721tumor celllines.3. The expression level of histone deacetylase, acetyl histone, apoptosis-relatedproteins and cell cycle proteins was deternined by western blotting assay.4. The apoptosis of C1204on K562cell was detected by flow cytometry.5. The H22mouse tumor xenograft models was established and antitumor effect ofC1204given by intragastric administration,intraperitoneal injection and tail veininjection was measured.RESULTS1. The curcumin derivative C1204can significantly inhibit the growth activity ofdifferent tumor cell lines with the average IC50value was less than10μg/mL;2. The forming of colonies of K562、HT-29、CNE2、SGC7901、SW620、SMMC7721tumor cell lines were apparently inhibite by the derivative C1204.3. The expression level of HDAC1and HDAC4was down-regulated by lowconcentration of C1204, on the contrary, the acetylation level of H3was up-regulate,the results of which include regulating the expressing of related gene and then inhibitthe grows of tumor cell. The derivative C1204can obviously also promote theexpression level of cycle related protein, like p21protein and the p53proteinexpression level was up-regulated in a dose-dependent manner, all of which reachedto block the cell cycle and made the cell inhibited. 4. The results of flow cytometry show that the derivative C1204can induce theapoptosis of K562cell to some degree.5.Animal experiments suggest that C1204showed significantly inhibition on H22ofmice in vivo. The inhibitory rates of200mg/kg and100mg/kg were48.35%and30.54%,respectively, by intragastric administration; The inhibitory rates of200mg/kg,100mg/kg and50mg/kg were60.91%、51.47%and45.47%, respectively, byintraperitoneal injection administration; while the inhibitory rates of50mg/kg was53.68%by tail vein injection administration.CONCLUSIONS1. The in vitro and in vivo data suggest that curcumin derivative C1204exhibited thepotential to be antitumor activities.2. To inhibit the expession level of histone deacetylases while up-regulate the acetylhistone maybe one of the the possible mechanisms of the inbibitory on K562ofC1204.3. To up-regulate the expression level of apoptosis-related proteins and promote cellcycle related proteins of C1204on tumor cell maybe the other commonmechanisms.