Abstract：
BACKGROUND: Scutellaria barbata D. Don (SB), commonly known as Ban Zhi Lian and firstly documented by Shigong Chen, is a dried whole plant that has been studied for its therapeutic effects on breast cancer, colon cancer, and prostate cancer. Among its various compounds, scutellarin (SCU) has been demonstrated with anti-tumor effects.
OBJECTIVE: This study aimed to evaluate the effects of SB water extract (SBW) and scutellarin on breast cancer stem cells (BCSCs), and to investigate their potential therapeutic effects on breast tumors in mice.
METHODS: BCSCs were enriched from human breast cancer cells (MDA-MB-231 and MDA-MB-361) and their characteristics were analyzed. The effects of varying concentrations of SBW and scutellarin on cell viability, proliferation, self-renewal, and migration abilities were studied, along with the underlying mechanisms. The in vivo anti-tumor effects of scutellarin were further evaluated in SCID/NOD mice. Firstly, mice were inoculated with naïve BCSCs and subjected to treatment with scutellarin or vehicle. Secondly, BCSCs were pre-treated with scutellarin or vehicle prior to inoculation into mice.
RESULTS: The derived BCSCs expressed CD44, CD133 and ALDH1, but not CD24, indicating that BCSCs have been successfully induced from both MDA-MB-231 and MDA-MB-361 cells. Both SBW and scutellarin reduced the viability, proliferation, sphere and colony formation, and migration of BCSCs. In mice with tumors derived from naïve BCSCs, scutellarin significantly reduced tumor growth, expression of proliferative (Ki67) and stem cell markers (CD44), and lung metastasis. In addition, pre-treatment with scutellarin also slowed tumor growth. Western blot results suggested the involvement of Wnt/β-catenin, NF-κB, and PTEN/Akt/mTOR signaling pathways underlying the inhibitory effects of scutellarin.
CONCLUSIONS: Our study demonstrated for the first time that both SB water extract and scutellarin could reduce the proliferation and migration of BCSCs in vitro. Scutellarin was shown to possess novel inhibitory activities in BCSCs progression. These findings suggest that Scutellaria barbata water extract, in particular, scutellarin, may have potential to be further developed as an adjuvant therapy for reducing breast cancer recurrence.
OBJECTIVE: This study aimed to evaluate the effects of SB water extract (SBW) and scutellarin on breast cancer stem cells (BCSCs), and to investigate their potential therapeutic effects on breast tumors in mice.
METHODS: BCSCs were enriched from human breast cancer cells (MDA-MB-231 and MDA-MB-361) and their characteristics were analyzed. The effects of varying concentrations of SBW and scutellarin on cell viability, proliferation, self-renewal, and migration abilities were studied, along with the underlying mechanisms. The in vivo anti-tumor effects of scutellarin were further evaluated in SCID/NOD mice. Firstly, mice were inoculated with naïve BCSCs and subjected to treatment with scutellarin or vehicle. Secondly, BCSCs were pre-treated with scutellarin or vehicle prior to inoculation into mice.
RESULTS: The derived BCSCs expressed CD44, CD133 and ALDH1, but not CD24, indicating that BCSCs have been successfully induced from both MDA-MB-231 and MDA-MB-361 cells. Both SBW and scutellarin reduced the viability, proliferation, sphere and colony formation, and migration of BCSCs. In mice with tumors derived from naïve BCSCs, scutellarin significantly reduced tumor growth, expression of proliferative (Ki67) and stem cell markers (CD44), and lung metastasis. In addition, pre-treatment with scutellarin also slowed tumor growth. Western blot results suggested the involvement of Wnt/β-catenin, NF-κB, and PTEN/Akt/mTOR signaling pathways underlying the inhibitory effects of scutellarin.
CONCLUSIONS: Our study demonstrated for the first time that both SB water extract and scutellarin could reduce the proliferation and migration of BCSCs in vitro. Scutellarin was shown to possess novel inhibitory activities in BCSCs progression. These findings suggest that Scutellaria barbata water extract, in particular, scutellarin, may have potential to be further developed as an adjuvant therapy for reducing breast cancer recurrence.
摘要：
背景：半枝莲D.唐（SB），俗称班志莲，最早由陈世公记载，是一种干燥的整株植物，已经对其对乳腺癌的治疗作用进行了研究，结肠癌,和前列腺癌。在它的各种化合物中，灯盏乙素（SCU）已被证明具有抗肿瘤作用。
目的：本研究旨在评估SB水提取物（SBW）和灯盏乙素对乳腺癌干细胞（BCSCs）的影响。并研究其对小鼠乳腺肿瘤的潜在治疗作用。
方法：从人乳腺癌细胞（MDA-MB-231和MDA-MB-361）中富集BCSCs并分析其特性。不同浓度的SBW和灯盏乙素对细胞活力的影响，扩散,自我更新,研究了迁移能力，以及潜在的机制。在SCID/NOD小鼠中进一步评估了灯盏乙素的体内抗肿瘤作用。首先,给小鼠接种初始BCSC,并用灯盏乙素或载体处理。其次,在接种入小鼠之前,用灯盏乙素或载体预处理BCSC。
结果:衍生的BCSC表达CD44、CD133和ALDH1,但不表达CD24,表明已经从MDA-MB-231和MDA-MB-361细胞成功诱导了BCSC。SBW和scutellarin都降低了生存能力，扩散,球体和菌落的形成，和BCSC的迁移。在患有源自原始BCSC的肿瘤的小鼠中，灯盏乙素显著降低肿瘤生长，增殖（Ki67）和干细胞标志物（CD44）的表达，和肺转移。此外,用灯盏乙素预处理也减缓了肿瘤的生长。Westernblot结果提示Wnt/β-catenin参与,NF-κB,和PTEN/Akt/mTOR信号通路是灯盏乙素抑制作用的基础。
结论：我们的研究首次证明SB水提取物和灯盏乙素均能降低BCSCs的体外增殖和迁移。灯盏乙素被证明在BCSC进展中具有新的抑制活性。这些发现表明半枝莲的水提取物，特别是,scutellarin,作为减少乳腺癌复发的辅助疗法，有可能进一步发展。
目的：本研究旨在评估SB水提取物（SBW）和灯盏乙素对乳腺癌干细胞（BCSCs）的影响。并研究其对小鼠乳腺肿瘤的潜在治疗作用。
方法：从人乳腺癌细胞（MDA-MB-231和MDA-MB-361）中富集BCSCs并分析其特性。不同浓度的SBW和灯盏乙素对细胞活力的影响，扩散,自我更新,研究了迁移能力，以及潜在的机制。在SCID/NOD小鼠中进一步评估了灯盏乙素的体内抗肿瘤作用。首先,给小鼠接种初始BCSC,并用灯盏乙素或载体处理。其次,在接种入小鼠之前,用灯盏乙素或载体预处理BCSC。
结果:衍生的BCSC表达CD44、CD133和ALDH1,但不表达CD24,表明已经从MDA-MB-231和MDA-MB-361细胞成功诱导了BCSC。SBW和scutellarin都降低了生存能力，扩散,球体和菌落的形成，和BCSC的迁移。在患有源自原始BCSC的肿瘤的小鼠中，灯盏乙素显著降低肿瘤生长，增殖（Ki67）和干细胞标志物（CD44）的表达，和肺转移。此外,用灯盏乙素预处理也减缓了肿瘤的生长。Westernblot结果提示Wnt/β-catenin参与,NF-κB,和PTEN/Akt/mTOR信号通路是灯盏乙素抑制作用的基础。
结论：我们的研究首次证明SB水提取物和灯盏乙素均能降低BCSCs的体外增殖和迁移。灯盏乙素被证明在BCSC进展中具有新的抑制活性。这些发现表明半枝莲的水提取物，特别是,scutellarin,作为减少乳腺癌复发的辅助疗法，有可能进一步发展。
