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首页> 外文期刊>Oncology letters >Berberine enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast cancer
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Berberine enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast cancer

机译：小Ber碱增强乳腺癌中与肿瘤坏死因子相关的凋亡诱导配体介导的细胞凋亡

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摘要

Berberine (BBR) has been used for the treatment of bacterial and fungal infections and also for cancer-associated symptoms such as diarrhea. Furthermore, it has been reported that BBR may have direct antitumor effects. Although evidence supports the theory that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising candidate for treating cancer, its usage may be limited due to the resistance to the TRAIL-induced apoptosis of cancer cells. In the present study, the effect of BBR on TRAIL-induced antitumor effects was investigated in vitro using recombinant TRAIL and in vivo using a 4T1 murine breast cancer model in combination with anti-DR5 (death-inducing TRAIL receptor) monoclonal antibody therapy. BBR sensitized human breast cancer cell lines to TRAIL-mediated apoptosis in vitro. The combination of BBR and recombinant TRAIL significantly activated caspase-3 and PARP cleavage in TRAIL-resistant MDA-MB-468 cells. Furthermore, BBR in combination with TRAIL more effectively induced apoptosis compared with coptisine (COP), which is structurally related to BBR. In a murine 4T1 breast cancer model, BBR treatment enhanced the efficacy of anti-DR5 antibody therapy against primary tumor growth and lung metastasis. Thus, BBR may become a new adjuvant for overcoming the resistance of cancer cells to TRAIL/DR5-mediated therapy.
机译：小ber碱（BBR）已用于治疗细菌和真菌感染，还用于治疗与癌症相关的症状，例如腹泻。此外，据报道，BBR可能具有直接的抗肿瘤作用。尽管有证据支持肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）是治疗癌症的有前途的理论，但由于对TRAIL诱导的癌细胞凋亡具有抗性，因此其使用可能受到限制。在本研究中，在体外使用重组TRAIL研究了BBR对TRAIL诱导的抗肿瘤作用的作用，并在体内使用4T1鼠乳腺癌模型与抗DR5（诱导死亡的TRAIL受体）单克隆抗体疗法进行了体内研究。 BBR在体外使人乳腺癌细胞系对TRAIL介导的细胞凋亡敏感。 BBR和重组TRAIL的组合可显着激活耐TRAIL的MDA-MB-468细胞中的caspase-3和PARP裂解。此外，与在结构上与BBR相关的黄连（COP）相比，BBR与TRAIL结合更有效地诱导了细胞凋亡。在鼠类4T1乳腺癌模型中，BBR治疗增强了抗DR5抗体治疗针对原发性肿瘤生长和肺转移的功效。因此，BBR可能成为克服癌细胞对TRAIL / DR5介导的治疗的耐药性的新佐剂。

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