Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness.
Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness.
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DOI：
10.21037/tcr-23-1885
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发表时间：
2023-12-31
影响因子：
0.9
通讯作者：
中科院分区：
文献类型：
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化疗是治疗乳腺癌的常用方法之一。肿瘤干细胞（cancer stem cells, CSCs）的诱导是化疗失败和乳腺癌复发的重要原因。黄芪甲苷（Astragaloside IV， ASIV）是中药黄芪的有效成分之一，能提高各种肿瘤对化疗药物的敏感性。本研究从CSCs的角度探讨asv对化疗药物紫杉醇（paclitaxel， PTX）在乳腺癌中的致敏作用。该研究包括体外和体内实验。成功地在体外诱导了具有干细胞特征的乳腺癌细胞系MCF7的CSCs。采用细胞计数试剂盒-8 （CCK-8）和集落形成法检测细胞活力和增殖，采用流式细胞术和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）法检测细胞凋亡。采用western blotting （WB）和免疫组化（IHC）检测stemness相关蛋白的表达。采用小鼠体重、组织病理学和脏器损伤监测药物毒性。干性标志物Sox2、Nanog和ALDHA1在MCF7- cscs中的表达强于MCF7。PTX通过促进细胞凋亡抑制肿瘤细胞的增殖，而乳腺癌干细胞（BCSCs）的干性则抵抗PTX的作用。asv降低BCSCs的干性，增加BCSCs对PTX的敏感性，协同促进PTX诱导的乳腺癌细胞凋亡。我们的研究结果显示，与单独使用PTX处理的BCSCs相比，添加ASIV后细胞总凋亡率提高了约25%。体内实验表明，ASIV增强了PTX抑制乳腺癌生长的能力。WB和IHC显示asv降低了CSCs的干性。在本研究中，乳腺癌对PTX的耐药归因于CSCs的存在；asv通过显著减弱乳腺癌干性标志，减弱MCF7-CSCs对PTX的耐药性，提高PTX的疗效。
Chemotherapy is one of the common treatments for breast cancer. The induction of cancer stem cells (CSCs) is an important reason for chemotherapy failure and breast cancer recurrence. Astragaloside IV (ASIV) is one of the effective components of the traditional Chinese medicine (TCM) Astragalus membranaceus, which can improve the sensitivity of various tumors to chemotherapy drugs. Here, we explored the sensitization effect of ASIV to chemotherapy drug paclitaxel (PTX) in breast cancer from the perspective of CSCs. The study included both in vitro and in vivo experiments. CSCs from the breast cancer cell line MCF7 with stem cell characteristics were successfully induced in vitro. Cell viability and proliferation were detected using the Cell Counting Kit-8 (CCK-8) and colony formation assays, and flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) methods were performed to detect cell apoptosis. Stemness-related protein expression was determined by western blotting (WB) and immunohistochemistry (IHC). Body weight, histopathology, and visceral organ damage of mice were used to monitor drug toxicity. The expression of stemness markers including Sox2, Nanog, and ALDHA1 was stronger in MCF7-CSCs than in MCF7. PTX treatment inhibited the proliferation of tumor cells by promoting cell apoptosis, whereas the stemness of breast cancer stem cells (BCSCs) resisted the effects of PTX. ASIV decreased the stemness of BCSCs, increased the sensitivity of BCSCs to PTX, and synergistically promoted PTX-induced apoptosis of breast cancer cells. Our results showed that the total cell apoptosis rate increased by about 25% after adding ASIV compared with BCSCs treated with PTX alone. The in vivo experiments demonstrated that ASIV enhanced the ability of PTX to inhibit the growth of breast cancer. WB and IHC showed that ASIV reduced the stemness of CSCs. In this study, the resistance of breast cancer to PTX was attributed to the existence of CSCs; ASIV weakened the resistance of MCF7-CSCs to PTX by significantly attenuating the hallmarks of breast cancer stemness and improved the efficacy of PTX.
影响因子：
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作者：
Li B;Yu J;Liu P;Zeng T;Zeng X
通讯作者：
Zeng X