Objective： Apoptosis is a reliable marker of chemotherapeutic efficacy. Olaparib and paclitaxel inhibit proliferation and induce apoptosis in a variety of cancers. We investigated the effects of paclitaxel combined w...Objective： Apoptosis is a reliable marker of chemotherapeutic efficacy. Olaparib and paclitaxel inhibit proliferation and induce apoptosis in a variety of cancers. We investigated the effects of paclitaxel combined with olaparib on apoptosis in breast cancer Bcap37 cells. Methods： Proliferation and apoptosis were detected by MTT assay and PI staining. Degradation of procaspase-3 and poly（ADP-ribose） polymerase （PARP） was analyzed by Western blotting. Results： Compared with paclitaxel alone, paclitaxel combined with 100 mg olaparib significantly reduced survival in Bcap37 cells at all tested treatment durations （P〈0.05）; inhibition increased with increasing olaparib dose and treatment time （P〈0.01）. Combined treatment yielded significantly higher rates of apoptosis （P〈0.05）, which also increased with time （P〈0.01）. Fluorescence micrographs showed that early and late apoptotic cells increased with treatment time. Pro-caspase-3 and PARP degradation was induced by paclitaxel and enhanced by olaparib in a dose-dependent manner. Thus, combined treatment was substantially more effective than treatment with paclitaxel alone. Conclusions： Our findings suggest that paclitaxel and olaparib inhibit breast cancer Bcap37 cell proliferation and induce apoptosis. Combined treatment further reduced cell growth and enhanced apoptosis, suggesting that this combination therapy may be a promising treaunent for breast cancer.展开更多
三阴性乳腺癌(triple-negative breast cancer,TNBC)是雌、孕激素受体和HER-2表达均为阴性的乳腺癌,侵袭性强,与其他分子分型乳腺癌相比复发率较高,生存率低。临床上内科治疗主要以化疗为主,随着对TNBC分子分型的深入探索,靶向治疗的研...三阴性乳腺癌(triple-negative breast cancer,TNBC)是雌、孕激素受体和HER-2表达均为阴性的乳腺癌,侵袭性强,与其他分子分型乳腺癌相比复发率较高,生存率低。临床上内科治疗主要以化疗为主,随着对TNBC分子分型的深入探索,靶向治疗的研究逐渐成为关注的焦点。近些年,多种靶向药物进入临床试验,取得一定疗效,不良反应相对较轻,部分药物已批准上市。本文将对TNBC的靶向治疗应用进展进行综述。展开更多
文摘Objective： Apoptosis is a reliable marker of chemotherapeutic efficacy. Olaparib and paclitaxel inhibit proliferation and induce apoptosis in a variety of cancers. We investigated the effects of paclitaxel combined with olaparib on apoptosis in breast cancer Bcap37 cells. Methods： Proliferation and apoptosis were detected by MTT assay and PI staining. Degradation of procaspase-3 and poly（ADP-ribose） polymerase （PARP） was analyzed by Western blotting. Results： Compared with paclitaxel alone, paclitaxel combined with 100 mg olaparib significantly reduced survival in Bcap37 cells at all tested treatment durations （P〈0.05）; inhibition increased with increasing olaparib dose and treatment time （P〈0.01）. Combined treatment yielded significantly higher rates of apoptosis （P〈0.05）, which also increased with time （P〈0.01）. Fluorescence micrographs showed that early and late apoptotic cells increased with treatment time. Pro-caspase-3 and PARP degradation was induced by paclitaxel and enhanced by olaparib in a dose-dependent manner. Thus, combined treatment was substantially more effective than treatment with paclitaxel alone. Conclusions： Our findings suggest that paclitaxel and olaparib inhibit breast cancer Bcap37 cell proliferation and induce apoptosis. Combined treatment further reduced cell growth and enhanced apoptosis, suggesting that this combination therapy may be a promising treaunent for breast cancer.
文摘目的:探讨大鼠大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)模型脑组织Th1/Th2细胞平衡与二磷酸腺苷核糖多聚酶-1(Poly(ADP-ribose)polymerase-1,PARP-1)表达是否存在相关性。方法:将健康雄性SD大鼠随机分成正常对照组、假手术组、模型组、PARP-1抑制剂PJ34组,按再灌注不同时间点分为6、12、24、48、72 h五个亚组,各组取材前进行神经功能损伤评分,氯化三苯基四氮唑(triphenyltetrazolium chloride,TTC)染色评价脑梗死体积,RT-PCR技术检测脑缺血/再灌注损伤病灶中PARP-1 m RNA的表达,Western Blot技术检测PARP-1聚合体蛋白的表达,ELISA技术测定干扰素-γ(interferon-γ,INF-γ)、白介素4(interleukin4,IL-4)水平。结果:与假手术组比,模型组神经功能损伤评分、脑梗死体积、PARP-1表达及炎性反应效应细胞(helper T cell 1,Th1)与辅助性效应细胞(helper T cell 2,Th2)的比值均显著增加(P<0.01);与模型组比,PJ34组梗死体积明显减小(P<0.01),PARP-1表达、Th1/Th2比值均显著降低(P<0.01);Th1/Th2与PARP-1水平呈显著正相关(r=0.984,P<0.05)。结论:MCAO大鼠脑组织Th1/Th2细胞平衡状态与PARP-1表达存在相关性。
文摘三阴性乳腺癌(triple-negative breast cancer,TNBC)是雌、孕激素受体和HER-2表达均为阴性的乳腺癌,侵袭性强,与其他分子分型乳腺癌相比复发率较高,生存率低。临床上内科治疗主要以化疗为主,随着对TNBC分子分型的深入探索,靶向治疗的研究逐渐成为关注的焦点。近些年,多种靶向药物进入临床试验,取得一定疗效,不良反应相对较轻,部分药物已批准上市。本文将对TNBC的靶向治疗应用进展进行综述。
