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Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Carboplatin Effects Against Ovarian Cancer

机译:罗非鱼提取物的抗肿瘤活性及卡铂对卵巢癌的增强作用

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Backgiound: Tumor resistance to platinum-based drugs has been an obstacle to the treatment of ovarian cancer. Extract of the plant Rauwolfia vomitoria has long been used by cancer patients. However, there have not been systematic studies of its anticancer activity.Objective: In an effort to enhance the effectiveness of platinum-based drugs, we investigated the anticancer effect of a Rauwolfia vomitoria extract (Rau), both alone and in combination with carboplatin (Cp).Methods: In vitro cytotoxicity and colony formation were evaluated in several ovarian cancer cell lines. In vivo effects were evaluated in an intraperitoneal ovarian cancer mouse model. The combination of Rau and Cp was assessed using Chou-Talalay's constant ratio design and median effect analysis based on the isobologram principle to determine the combination index values.Results: Rau decreased cell growth in all 3 tested ovarian cancer cell lines dose dependently and completely inhibited formation of colonies in soft agar. Apoptosis was induced in a time- and dose-dependent manner and was the predominant form of Rau-induced cell death. Synergy of Rau with Cp was detected, with combination index values < 1 and dose reduction index values for Cp ranging from 1.7- to 7-fold. Tumor growth in mice was significantly suppressed by 36% or 66% with Rau treatment alone at a low (20 mg/kg) or a high dose (50 mg/kg), respectively, an effect comparable to that of Cp alone. The volume of ascitic fluid and the number of nonblood cells in ascites were also significantly decreased. Combining Rau with Cp remarkably enhanced the effect of Cp and reduced tumor burden by 87% to 90% and ascites volume by 89% to 97%.Conclusions: Rau has potent antitumor activity and in combination significantly enhances the effect of Cp against ovarian cancer.
机译:背景:肿瘤对铂类药物的耐药性一直是卵巢癌治疗的障碍。癌症患者长期以来一直使用植物紫罗兰的提取物。然而,尚未对其抗癌活性进行系统研究。目的:为了增强铂基药物的有效性,我们研究了紫罗兰(Rauwolfia vomitoria)提取物(Rau)单独或与卡铂联合使用的抗癌作用(方法:在几种卵巢癌细胞系中评估体外细胞毒性和集落形成。在腹膜内卵巢癌小鼠模型中评估了体内作用。使用Chou-Talalay的恒比设计和基于等效线图原理的中值效应分析来评估Rau和Cp的组合,以确定组合指数值。结果:Rau在所有3种受测试的卵巢癌细胞系中均依赖剂量并完全抑制了其生长在软琼脂中形成菌落。凋亡以时间和剂量依赖性方式被诱导,并且是Rau诱导的细胞死亡的主要形式。检测到Rau与Cp的协同作用,组合指数值<1,Cp的剂量降低指数值在1.7到7倍之间。仅在低(20 mg / kg)或高剂量(50 mg / kg)的单独Rau治疗下,小鼠的肿瘤生长被显着抑制了36%或66%,其效果可与单独Cp相媲美。腹水中的腹水量和非血细胞数量也明显减少。 Rau与Cp的结合显着增强了Cp的作用,并将肿瘤负荷降低了87%至90%,腹水量降低了89%至97%。结论:Rau具有强大的抗肿瘤活性,并且联合使用可显着增强Cp对抗卵巢癌的作用。

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