Background: 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. Methods: 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. Results: 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. Conclusions: 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.
基金：
National Natural Science Foundation of China [81974571]; Guangdong Basic and Applied Basic Research Foundation [2022A1515110859]
第一作者机构：[1]Guangzhou Univ Chinese Med, Affiliated Hosp 2, State Key Lab Tradit Chinese Med Syndrome, 55 N Neihuanxi Rd, Guangzhou 510006, Peoples R China[2]Guangdong Prov Hosp Chinese Med, Dept Breast, 111 N Dade Rd, Guangzhou 510120, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Guangzhou Univ Chinese Med, Affiliated Hosp 2, State Key Lab Tradit Chinese Med Syndrome, 55 N Neihuanxi Rd, Guangzhou 510006, Peoples R China[2]Guangdong Prov Hosp Chinese Med, Dept Breast, 111 N Dade Rd, Guangzhou 510120, Peoples R China[3]Guangdong Acad Chinese Med, 55 N Neihuanxi Rd, Guangzhou 510006, Peoples R China[10]Zhejiang Univ, Sch Med, 866 Yuhangtang Rd, Hangzhou 310006, Peoples R China[*1]State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of[*2]Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, 111 N, Dade Road, Guangzhou 510120, China[*3]Guangdong Academy of Chinese Medicine, 55 N, Neihuanxi Road, Guangzhou 510006, China[*4]Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China
推荐引用方式(GB/T 7714)：
Huang Ping,Li Huachao,Ren Liping,et al.Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness[J].TRANSLATIONAL CANCER RESEARCH.2023,12(12):doi:10.21037/tcr-23-1885.
APA：
Huang, Ping,Li, Huachao,Ren, Liping,Xie, Haimei,Chen, Liushan...&Chen, Qianjun.(2023).Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness.TRANSLATIONAL CANCER RESEARCH,12,(12)
MLA：
Huang, Ping,et al."Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness".TRANSLATIONAL CANCER RESEARCH 12..12(2023)
