Effect of arsenic trioxide on multidrug resistant hepatocellular carcinoma cells.
Our previous study showed that arsenic trioxide (As2O3) was effective in inhibiting the growth of human hepatocellular carcinoma (HepG2) cells via induction of apoptosis. In the present study, we examined the effect of As2O3 on multidrug resistant human hepatocellular carcinoma (R-HepG2) cells which are characterized with overexpression of mdr1 gene and P-glycoprotein. The anti-proliferation of R-HepG2 by As2O3 was examined by MTT assay. For the induction of apoptosis, DNA fragmentation and Annexin V-PI staining were performed after treatment with arsenic trioxide. To study the effect of arsenic trioxide on P-glycoprotein, Western analysis probing anti-P-glycoprotein antibody was used to monitor the change of its expression. Results showed that As2O3 was effective in inhibiting the cell proliferation of R-HepG2 cells in a dose- and time-dependent manner via induction of apoptosis without affecting the cell cycle. The sensitivity of R-HepG2 cells toward As2O3 was found to be similar to that of the parental HepG2 cells. The Western analysis showed that As2O3 was probably not the substrate to be bound and extruded by P-glycoprotein in R-HepG2 cells because it could not maintain the cellular P-glycoprotein expression.
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Judy Yuet-Wa
JY
Chan
Katy Pak-Yan
KP
Siu
Kwok-Pui
KP
Fung
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D010087:Oxides / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D004317:Doxorubicin; D000077237:Arsenic Trioxide