Growth-inhibiting effects of taxol on human liver cancer in vitro and in nude mice

Abstract

AIM To investigate the effects of taxol onSMMC-7721 human hepatoma and itsmechanisms.METHODS In vitro cell growth was assessedby trypan blue exclusion method.Experimentalhepatoma model was established by seedingSMMC-7721 cells subcutaneously into Balb/c(nu/nu)nude mice.In vivo tumor growth wasdetermined by measurement of tumor diameterwith Vernier calipers.The syntheses of DNA,RNA and protein were analyzed by incorporationof ~3H-thymidine,~3H-uridine and ~3H-leucinerespectively.Using light and electronmicroscopes to observe the morphologicalchanges of cells including mitosis andapoptosis.RESULTS Taxol was effective against SMMC-7721 human hepatoma cell growth in the rangesof 2.5 nmol/L-10 nmol/L with mitotic arrestand apoptosis in vitro.DNA,RNA and proteinsyntheses in cells were also obviouslysuppressed by in vitro treatment of taxol for72 h.Taxol at 2.5 nmol/L reduced ~3H-thymidineuptake to about 34% of the control value(P<0.05).Increasing the dose of taxol to20 nmol/L resulted in a greater decrease in ~3H-thymidine incorporation to 60% of the controlvalue(P<0.01).At a concentration of 20 nmol/L,the ~3H-uridine and ~3H-leucine uptakeswere reduced to 52%(P<0.05)and 63%(P<0.01),respectively.In vivo,taxolsignificantly inhibited SMMC-7721 tumor growthat 10 mg/kg,i.p.,once daily for 10 d.A morethan 90% decrease in tumor volume wasobserved by day 11(P<0.01)similarly withmitotic arrest and cell apoptosis.CONCLUSION Taxol has a marked anticanceractivity in SMMC-7721 human hepatoma both invitro and in nude mice.Its mechanisms might beassociated with mitotic arrest,subsequently,apoptosis of the hepatoma cells.No obvioustoxicity was observed with in vivoadministration of taxoi.