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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Proanthocyanidin from grape seeds enhances doxorubicin-induced antitumor effect and reverses drug resistance in doxorubicin-resistant K562/DOX cells.
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Proanthocyanidin from grape seeds enhances doxorubicin-induced antitumor effect and reverses drug resistance in doxorubicin-resistant K562/DOX cells.

机译:葡萄籽中的原花青素增强了阿霉素诱导的抗肿瘤作用,并逆转了对阿霉素耐药的K562 / DOX细胞的耐药性。

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With the aim of enhancing the efficacy of chemotherapeutic agents, we investigated the antitumor actions and reversal effect on drug resistance of proanthocyanidin plus doxorubicin. The results showed that proanthocyanidin 12.5~200 mg/L significantly inhibited proliferation of K562, K562/DOX, SPC-A-1, and Lewis cells in vitro in a time- and concentration-dependent manner, as determined by microculture tetrazolium assay. A combination of proantho cyani din 12.5, or 25 mg/L and doxorubicin treatment synergistically inhibited cell proliferation with decreased IC50 values. Proanthocyanidin reverses drug resistance in doxorubicin-resistant K562/DOX cells, and IC50 values were decreased by 9.19 (3.64~23.19), 2.56 (1.48~4.44), and 0.94 (0.81~1.09) mg/L, respectively, after 24 h treatment with doxorubicin 0.1~9.0 mg/L alone or in combination with proanthocyanidin 12.5 or 25 mg/L; the proanthocyanidin reversal fold was 3.6 and 9.8, respectively. Under confocal laser scanning microscope, the combination of proanthocyanidin 25 or 50 mg/L with doxorubicin 3 mg/L significantly increased the accumulation of intracellular doxorubicin, Ca2+, and Mg2+, and reduced the pH value and mitochondrial membrane potential in K562/DOX cells as compared with doxorubicin alone (p < 0.01). Additionally, the apoptosis rate was increased by 11.3% +/- 3.3%, 14.2% +/- 5.4%, and 23.8% +/- 2.8%, respectively, for doxorubicin 3 mg/L alone or with proanthocyanidin 12.5 or 25 mg/L, as compared with controls (3.0% +/- 1.4%), as demonstrated by flow cytometry. In vivo experiments demonstrated that i.p. administration of proanthocyanidin 10 mg/kg with doxorubicin 2 mg/kg had an inhibitory effect on the growth of transplantation tumor sarcoma 180 and hepatoma 22 in mice as compared with doxorubicin alone (p < 0.05). These results suggest that proanthocyanidin enhances doxorubicin-induced antitumor effect and reverses drug resistance, and its mechanism is attributed partially to the promotion of doxorubicin-induced apoptosis through an elevation of intracellular doxorubicin, and Ca2+, Mg2+ concentration, and a reduction of pH value and mitochondrial membrane potential.
机译:为了增强化学治疗剂的功效,我们研究了原花青素和阿霉素的抗肿瘤作用和对耐药性的逆转作用。结果表明,原花青素12.5〜200 mg / L可以在体外以时间和浓度依赖性方式显着抑制K562,K562 / DOX,SPC-A-1和Lewis细胞的增殖,这是通过微培养四唑法测定的。原花青素12.5或25 mg / L与阿霉素的组合可协同抑制细胞增殖,降低IC50值。原花青素逆转阿霉素耐药性K562 / DOX细胞的耐药性,治疗24小时后,IC50值分别降低9.19(3.64〜23.19),2.56(1.48〜4.44)和0.94(0.81〜1.09)mg / L。阿霉素0.1〜9.0 mg / L单独使用或与原花青素12.5或25 mg / L联合使用;原花色素逆转倍数分别为3.6和9.8。在共聚焦激光扫描显微镜下,原花青素25或50 mg / L与阿霉素3 mg / L的组合显着增加了细胞内阿霉素,Ca2 +和Mg2 +的积累,并降低了K562 / DOX细胞的pH值和线粒体膜电位。与单独的阿霉素相比(p <0.01)。此外,单独使用阿霉素3 mg / L或与原花青素12.5或25 mg / L相比,凋亡率分别提高了11.3%+/- 3.3%,14.2%+/- 5.4%和23.8%+/- 2.8%。如通过流式细胞术证明的,与对照(3.0%+ /-1.4%)相比,L。体内实验表明与单独的阿霉素相比,给予10 mg / kg的原花青素和2 mg / kg的阿霉素对小鼠移植瘤肉瘤180和肝癌22的生长具有抑制作用(p <0.05)。这些结果表明原花青素增强了阿霉素诱导的抗肿瘤作用并逆转了耐药性,其机理部分归因于通过细胞内阿霉素,Ca2 +,Mg2 +浓度的升高以及pH值和pH值的降低促进了阿霉素诱导的细胞凋亡。线粒体膜电位。

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