脱氢枞胺对氟苯甲醛对人肝癌细胞的抑制作用
Inhibitory Effect of Dehydroabietylamine-Fluorobenzaldehyde on Human Hepatocellular Carcinoma Cells
1-(7-异丙基-1 / 4a-二甲基-1 / 2 / 3 / 4 / 4a / 9 / 10 / 10a-八氢菲基-1-yl)-N-(4-氟苯亚甲基)甲胺 / 脱氢枞胺对氟苯甲醛 / 凋亡 / 线粒体 / 肝癌 {{custom_keyword}} /
To examine the anti-proliferation effects of a novel derivative of dehydroabietylamine, dehydroabietylamine-fluorobenzaldehyde / on human hepatocellular carcinoma cells and to expolore its molecular mechanism. METHODS??MTT assay was adopted to detect the proliferation status of the cells treated with DHAA-F； cellular apoptosis and reduction of mitochondria membrane potential (Δψm) were analyzed using flow cytometry (FCM)； Western blotting assay was used to evaluate the release of Cyt c, and the expressions of p53, Bcl-2 and Bax protein； and the caspase-3 activity was determined with fluorescence spectrophotometry. To evaluate the anti-tumor effect of DHAA-F in vivo, mouse model bearing inoculated H22 tumor was established. RESULTS??DHAA-F strongly inhibited human hepatoma cells proliferation. The IC50 value of DHAA-F was （44.47±2.15）μmol·L-1 for SMMC-7721, （48.64±1.76）μmol·L-1 for Bel-7402, and （52.83±2.25）μmol·L-1 for HepG2. DHAA-F displayed a significant inhibitory effect on the growth of SMMC-7721 cells in a dose- and time-dependent manner. When SMMC-7721 cells were pretreated with DHAA-F for 24 h, the apoptosis rate significantly increase and the mitochondrial membrane potential significantly decreased. Western blotting assay showed significant decrease of Bcl-2 protein expression and increase of Bax, p53 protein expression, cytosol Cyt c level and caspase-3 activity. DHAA-F could significantly reduce tumor weight in the H22 solid tumor mouse model in vivo. CONCLUSION??These findings suggest that DHAA-F has potent antitumor activity both in vivo and in vitro and the mechanism may be related to the apoptosis induced by DHAA-F through a mitochondrial pathway. {{custom_keyword}} /
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