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Abstract：
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and poor prognosis. Meanwhile, doxorubicin, a chemotherapeutic agent for triple-negative breast cancer, has poor sensitivity. The objective of this study was to examine the effect of cordycepin on doxorubicin sensitivity and efficacy in the TNBC xenograft model and explore the relevant molecular pathways. The combination of the drugs in nude mice carrying MDA-MB-231 xenografts significantly reduced the volume, size, and weight of xenografts and improved the tumor inhibition rate. The drug combination was significantly more effective than cordycepin or doxorubicin alone, reflecting the fact that cordycepin enhanced the anti-tumor effects of doxorubicin in MDA-MB-231 xenografts. At the same time, the monitoring of several biological parameters failed to detect any obvious side effects associated with this treatment. After predicting the importance of the TNF pathway in inhibiting tumor growth using network pharmacology methods, we verified the expression of TNF pathway targets via immunohistochemistry and quantitative PCR. Furthermore, a TNF-α inhibitor was able to abrogate the beneficial effects of cordycepin and doxorubicin treatment in MDA-MB-231 cells. This clearly indicates the role of TNF-α, or related molecules, in mediating the therapeutic benefits of the combined treatment in animals carrying TNBC xenografts. The observations reported here may present a new direction for the clinical treatment of TNBC.
摘要：
三阴性乳腺癌(TNBC)是一种死亡率高、预后差的乳腺癌亚型。同时,阿霉素,治疗三阴性乳腺癌的化疗药物,灵敏度差。本研究的目的是检查虫草素对TNBC异种移植模型中阿霉素敏感性和功效的影响，并探索相关的分子途径。在携带MDA-MB-231异种移植物的裸小鼠中，药物的组合显着减少了体积，尺寸,和移植瘤的重量和提高抑瘤率。该药物组合比单独使用虫草素或阿霉素明显更有效，这反映了虫草素增强了阿霉素在MDA-MB-231异种移植物中的抗肿瘤作用。同时,对几个生物学参数的监测未能发现与该治疗相关的任何明显副作用.在使用网络药理学方法预测TNF途径在抑制肿瘤生长中的重要性之后，我们通过免疫组织化学和定量PCR验证了TNF通路靶点的表达。此外，TNF-α抑制剂能够消除虫草素和阿霉素对MDA-MB-231细胞的有益作用。这清楚地表明了TNF-α的作用，或相关分子，在介导携带TNBC异种移植物的动物中联合治疗的治疗益处。本文报道的观察结果可能为TNBC的临床治疗提供新的方向。
