肿瘤细胞治疗研究
英文原题：Cannabidiol sensitizes triple-negative breast cancer cells to NK cell-mediated killing via EGFR inhibition and FAS upregulation.
Cannabidiol sensitizes triple-negative breast cancer cells to NK cell-mediated killing via EGFR inhibition and FAS upregulation.
这些发现表明，CBD通过破坏EGFR信号传导并促进凋亡，有望成为TNBC的潜在抗癌药物。然而，仍需进一步研究以优化其治疗窗并尽量减少不良反应，特别是关于其对免疫细胞的潜在细胞毒性。
三阴性乳腺癌（TNBC）是一种高度侵袭性的亚型，缺乏靶向治疗，临床上面临重大挑战。表皮生长因子受体（EGFR）在TNBC进展中发挥关键作用，使其成为治疗干预的有前景靶点。本研究探讨了大麻二酚（CBD）作为靶向TNBC中EGFR及相关信号通路的治疗药物的潜力。
TNBC细胞系MDA-MB-468和MDA-MB-231在有或无表皮生长因子（EGF）存在的条件下用CBD处理。评估了细胞增殖、FAS蛋白表达以及EGFR信号通路的激活情况。还评估了CBD对TNBC细胞和自然杀伤（NK）细胞的细胞毒性作用。
与单独EGF处理相比，CBD显著提高了MDA-MB-468细胞中FAS蛋白的表达（125.29 5.87% vs. 83.07 1.30%，p < 0.0001）。进一步的分子分析显示，CBD通过下调关键致癌蛋白（包括KRAS、PI3K和AKT）抑制EGFR信号传导。此外，CBD增强了NK-92细胞的细胞毒性作用，比单独EGF更有效地降低了MDA-MB-468细胞的活力（52.12 1.28% vs. 113.69 1.68%，p < 0.0001）。
BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive subtype lacking targeted therapies, presenting a significant clinical challenge. The epidermal growth factor receptor (EGFR) plays a crucial role in TNBC progression, making it a promising target for therapeutic intervention. This study investigated the potential of cannabidiol (CBD) as a therapeutic agent that targets EGFR and associated signaling pathways in TNBC. METHODS: The TNBC cell lines MDA-MB-468 and MDA-MB-231 were treated with CBD in the presence or absence of epidermal growth factor (EGF). Cell proliferation, FAS protein expression, and activation of the EGFR signaling pathway were assessed. The cytotoxic effects of CBD on TNBC cells and natural killer (NK) cells were also evaluated. RESULTS: CBD significantly elevated FAS protein expression in MDA-MB-468 cells compared to EGF treatment alone (125.29 5.87% vs. 83.07 1.30%, p < 0.0001). Further molecular analysis revealed that CBD inhibited EGFR signaling by downregulating key oncogenic proteins, including KRAS, PI3K, and AKT. Moreover, CBD enhanced the cytotoxic effects of NK-92 cells, reducing the viability of MDA-MB-468 cells more effectively than EGF alone did (52.12 1.28% vs. 113.69 1.68%, p < 0.0001). CONCLUSIONS: These findings suggest that CBD holds promise as a potential anticancer agent in TNBC by disrupting EGFR signaling and promoting apoptosis. However, further studies are necessary to optimize its therapeutic window and minimize adverse effects, particularly regarding its potential cytotoxicity to immune cells.
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