The effect of megestrol acetate on growth of HepG2 cells in vitro and in vivo.
OBJECTIVE
Hepatocellular carcinoma (HCC) is generally considered as a sex hormone-dependent tumor, and hormonal therapy has been proposed as a strategy for the treatment of HCC. The aim of the study is to investigate the effect of megestrol acetate, a synthetic progesteronal agent, on growth of HepG2 cells in vitro and in vivo.


METHODS
Cell growth in vitro was assessed by a colormetric method, and cell growth in vivo was assessed by tumor volumetrics.


RESULTS
Megestrol acetate was shown to inhibit the growth of HepG2 cells in vitro in dose- and time-dependent manners with an IC (50) of 260 microm (24-h incubation). The growth of HepG2 cell-transplanted tumors in nude mice was also inhibited by i.p. injection of megestrol acetate (10 mg/kg/day). The tumor volumes of the megestrol acetate-treated group regressed to 59% of controls by week 6 and to 41% of controls by week 13. Apoptosis following G(1) arrest was observed in megestrol acetate-treated cells and may be a mechanism through which megestrol acetate inhibits HepG2 cells. Megestrol acetate was also demonstrated to have a beneficial effect on the weight gain of tumor-bearing nude mice, and the mean weight of the megestrol acetate-treated animals was higher than that of controls from week 4 of the treatment period, and the differences were statistically significant in week 5 and 6 (P < 0.05, compared with controls). No significant survival advantage was, however, demonstrated in the treatment group.


CONCLUSIONS
This study showed that megestrol acetate inhibited the growth of HepG2 cells grown in vitro and in vivo. These data provide useful information for clinical study of megestrol acetate for the treatment of HCC.
Department of Experimental Surgery and Department of General Surgery, Singapore General Hospital, Singapore. geskai@sgh.com.sg
Kai
K
Zhang
Pierce K H
PK
Chow
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003124:Colorimetry; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy*; D019290:Megestrol Acetate / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D013997:Time Factors
D013256:Steroids; D011374:Progesterone; D019290:Megestrol Acetate