Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
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Piperlongumine 通过抑制三阴性乳腺癌中的 JAK2-STAT3 通路来诱导细胞凋亡并与多柔比星产生协同作用
DOI：
10.3390/molecules24122338
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发表时间：
2019-06-02
期刊：
影响因子：
4.6
通讯作者：
Yin, Yue
中科院分区：
文献类型：
--
作者：
Chen, Di;Ma, Yangmin;Yin, Yue
三阴性乳腺癌（TNBC）缺乏主要有效的靶分子，化疗仍然是目前的主要治疗方法。然而，传统的化疗药物，如阿霉素（DOX），副作用严重，预后差。胡椒碱是一种具有选择性抗癌作用的天然生物碱，有望成为治疗TNBC的新策略。在我们的研究中，我们建立了细胞活力、集落形成、流式细胞术、Western blot和肿瘤异种移植模型分析来评估PL和DOX单独和联合使用的抑制作用。数据显示，PL能有效抑制两种TNBC细胞株的细胞生长并诱导细胞凋亡。我们还首次证明了PL和DOX联合治疗可协同抑制TNBC细胞生长并诱导细胞凋亡。抑制STAT3激活被认为是其抗癌作用的机制之一。此外，这种组合的有效性在肿瘤异种移植模型中得到证实。这些结果表明，当单独使用PL或与DOX联合使用时，抑制JAK2-STAT3通路是一个关键的抗癌机制，这表明PL与化疗药物联合使用可能是临床治疗TNBC的一种潜在策略。
Triple-negative breast cancer (TNBC) lacks major effective target molecules and chemotherapy remains the current main treatment. However, traditional chemotherapy drugs, such as doxorubicin (DOX), cause serious side effects and have a poor prognosis. Piperlongumine (PL), a natural alkaloid, has showed selective anticancer effects and is expected to become a new strategy against TNBC. In our research, cell viability, colony formation, flow cytometry, Western blot, and tumor xenograft model assays were established to evaluate the suppression effect of PL and DOX alone and in combination. Data showed that PL could effectively inhibit cell growth and induce apoptosis in two TNBC cell lines. We also demonstrated for the first time that the combination treatment of PL and DOX synergistically inhibited cell growth and induced apoptosis in TNBC cells. The suppression of STAT3 activation was indicated to be a mechanism of the anticancer effect. Moreover, the effectiveness of this combination was confirmed in a tumor xenograft model. These results revealed that inhibition of the JAK2-STAT3 pathway was a key anticancer mechanism when treated with PL alone or combined with DOX, suggesting that the combination of PL and chemotherapy drugs may be a potential strategy for the clinical treatment of TNBC.