Tamoxifen inhibits proliferation and induces apoptosis in human hepatocellular carcinoma cell line HepG2 via down-regulation of survivin expression.
Tamoxifen has been used in patients with hepatocellular carcinoma (HCC). However, its inhibitory mechanism remains unknown. In current study, we evaluated the effect of tamoxifen on the estrogen receptor-alpha-negative HCC cell proliferation, apoptosis and expression of survivin which had been known to play an important role in promotion of cellular proliferation as well as inhibition of apoptosis in cancer cells. HepG2 cells were incubated with tamoxifen (0.1, 1, 10, or 20 microM) for up to 72 h. Cell proliferation was assessed, flow cytometric analysis was performed, and survivin expression was detected. Our results are showed as follows. Ten or 20 microM tamoxifen induced a reduction of cell proliferation. Basically reduction of proliferation was related to an increase in the fraction of G0/1-phase. When tamoxifen was administrated at higher concentration (20 microM), the increase of the relative apoptosis appeared with a delay, augmenting the effect of tamoxifen on cell proliferation. When apoptosis was induced, a significant depression of survivin expression preceded. In conclusion, the tamoxifen decreasing cell proliferation and induction of apoptosis of HepG2 cells depends on drug concentration, which is due to cytostatic and cytocide effects, the latter may be mediated by a down-regulation of survivin expression.
Guo
Renhua
R
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing 210029, PR China. rhguo@njmu.edu.cn
Huang
Zuhu
Z
Shu
Yongqian
Y
Jin
Shidai
S
Ge
Hongmei
H
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000077022:Survivin; D013629:Tamoxifen / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D013629:Tamoxifen