腹腔与静脉应用托泊替坎治疗人卵巢癌细胞株SKOV3裸小鼠网膜移植瘤的疗效比较(英文)

Comparison of efficacy and toxicity profile between intraperitoneal and intravenous topotecan in human ovarian cancer xenografts

Objective:To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice.Methods: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg×2, 3.0 mg/kg×2, 6.0 mg/kg×2 or 10.0 mg/kg×1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg×2 or 10.0 mg/kg×1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis.Results: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation.Conclusion:The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.

Objective：To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice. Methods： Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups （n=10）. Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells $KOV3 in athymie mice. Onset of intraperitoneal treatment with either topotecan or eisplatin （7.5 mg/kg） was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan （ 1.5 mg/kg × 2, 3.0 mg/kg × 2, 6.0 mg/ kg × 2 or 10.0 mg/kg×1 ）. Animals scheduled for topoteean i.v. received inLravenous administration of topotecan （6.0 mg/kg × 2 or 10.0 mg/kg ×1 ）. Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apopto- sis after drug administration was determined by flow cytometric analysis. Results： In a panel of ten tumour xenografts, intraperitoneal topoteean was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after bltraperltoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day （1 day） schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topoteean and eisplatin induce cells G0-GI arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in tcrm of apoptosis and cell cycle perturbation. Conclusion：The results may have implications for the future design of clinical studies on intraperitoneal application of topoteean. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topoteean administration.