Abstract：
BACKGROUND: Despite various treatment modalities, the progression and metastasis of breast cancer (BC) are grave concerns due to the alarming disease-free survival rate (DFS) and overall survival rate (OS) of affected patients. Over the years, many antibiotics, synthetic compounds, medicinal plant isolates and polyherbal combinations have been used as adjuvants in therapy for the management of primary and secondary tumors. Paclitaxel (PTX)-based chemotherapy for breast cancer causes multiple adverse side effects in patients. Withania somnifera (L.) Dunal (WS) and Asparagus racemosus Willd. (AR) as Ayurveda-inspired plant-based adjuvants were investigated for their anticancer effects on MDA-MB-231 and 4T1 cells in mouse model systems.
OBJECTIVE: This study focused on evaluating the adjuvant properties of WS and AR plant extracts with PTX and their effectiveness over PTX alone in terms of tumor inhibition.
METHODS: The effects of WS and AR on DNA double-strand breaks (DSBs), senescence induction and mitochondrial functions were evaluated in BC cells in vitro. The potential for cancer stem cell (CSC) inhibition was evaluated via mammosphere formation assays and CD44/CD24 immunostaining. In vivo tumor growth studies were conducted in athymic BALB/c mice for MDA-MB-231 cells and in BALB/c mice for 4T1 cells.
RESULTS: Induction of senescence was evident due to DSBs induced by the WS and AR extracts. Mammosphere formation and CD44/CD24 CSC markers were reduced after treatment with WS, AR or the combination of both in MCF-7 cells. WS or AR inhibited epithelial-to-mesenchymal transition (EMT). In vivo studies demonstrated that tumor growth inhibition was more pronounced in the treated group than in the PTX alone group and the untreated control group.
CONCLUSIONS: Our study showed that the use of WS or AR plant hydroalcoholic extracts in combination with paclitaxel (PTX) has better effects on sensitivity and efficacy than PTX alone, as demonstrated in in vitro BC cells and mouse models with BC cell grafts. Hence, scheduling adjuvant therapy with WS or AR alone or combined with PTX can be advantageous for the management of triple-negative BC (TNBC). Further studies are warranted in human clinical conditions to ascertain the efficacy of these treatments.
OBJECTIVE: This study focused on evaluating the adjuvant properties of WS and AR plant extracts with PTX and their effectiveness over PTX alone in terms of tumor inhibition.
METHODS: The effects of WS and AR on DNA double-strand breaks (DSBs), senescence induction and mitochondrial functions were evaluated in BC cells in vitro. The potential for cancer stem cell (CSC) inhibition was evaluated via mammosphere formation assays and CD44/CD24 immunostaining. In vivo tumor growth studies were conducted in athymic BALB/c mice for MDA-MB-231 cells and in BALB/c mice for 4T1 cells.
RESULTS: Induction of senescence was evident due to DSBs induced by the WS and AR extracts. Mammosphere formation and CD44/CD24 CSC markers were reduced after treatment with WS, AR or the combination of both in MCF-7 cells. WS or AR inhibited epithelial-to-mesenchymal transition (EMT). In vivo studies demonstrated that tumor growth inhibition was more pronounced in the treated group than in the PTX alone group and the untreated control group.
CONCLUSIONS: Our study showed that the use of WS or AR plant hydroalcoholic extracts in combination with paclitaxel (PTX) has better effects on sensitivity and efficacy than PTX alone, as demonstrated in in vitro BC cells and mouse models with BC cell grafts. Hence, scheduling adjuvant therapy with WS or AR alone or combined with PTX can be advantageous for the management of triple-negative BC (TNBC). Further studies are warranted in human clinical conditions to ascertain the efficacy of these treatments.
摘要：
背景：尽管有各种治疗方式，由于患者的无病生存率(DFS)和总生存率(OS)惊人,乳腺癌(BC)的进展和转移是人们严重关注的问题.多年来,许多抗生素，合成化合物，药用植物分离株和多草药组合已被用作治疗原发性和继发性肿瘤的佐剂。基于紫杉醇（PTX）的乳腺癌化疗会导致患者多种不良副作用。有忧郁症（L.)杜纳尔(WS)和芦笋。（AR）作为阿育吠陀启发的基于植物的佐剂，在小鼠模型系统中研究了它们对MDA-MB-231和4T1细胞的抗癌作用。
目的：这项研究的重点是评估WS和AR植物提取物与PTX的佐剂特性及其在抑制肿瘤方面相对于单独PTX的有效性。
方法：WS和AR对DNA双链断裂（DSB）的影响，在体外评估BC细胞的衰老诱导和线粒体功能。通过乳腺球团形成测定和CD44/CD24免疫染色评估癌症干细胞(CSC)抑制的潜力。在无胸腺BALB/c小鼠中进行MDA-MB-231细胞和在BALB/c小鼠中进行4T1细胞的体内肿瘤生长研究。
结果：由于WS和AR提取物诱导的DSBs，衰老的诱导是明显的。用WS治疗后，乳球形成和CD44/CD24CSC标志物减少，MCF-7细胞中的AR或两者的组合。WS或AR抑制上皮-间质转化(EMT)。体内研究表明,肿瘤生长抑制在治疗组中比在PTX单独组和未治疗对照组中更显著。
结论：我们的研究表明，与紫杉醇（PTX）联合使用WS或AR植物水醇提取物比单独使用PTX具有更好的敏感性和疗效。如在体外BC细胞和具有BC细胞移植物的小鼠模型中所证明的。因此，安排WS或AR单独或与PTX联合的辅助治疗对于三阴性BC(TNBC)的管理可能是有利的.需要在人类临床病症中进行进一步的研究以确定这些治疗的功效。
目的：这项研究的重点是评估WS和AR植物提取物与PTX的佐剂特性及其在抑制肿瘤方面相对于单独PTX的有效性。
方法：WS和AR对DNA双链断裂（DSB）的影响，在体外评估BC细胞的衰老诱导和线粒体功能。通过乳腺球团形成测定和CD44/CD24免疫染色评估癌症干细胞(CSC)抑制的潜力。在无胸腺BALB/c小鼠中进行MDA-MB-231细胞和在BALB/c小鼠中进行4T1细胞的体内肿瘤生长研究。
结果：由于WS和AR提取物诱导的DSBs，衰老的诱导是明显的。用WS治疗后，乳球形成和CD44/CD24CSC标志物减少，MCF-7细胞中的AR或两者的组合。WS或AR抑制上皮-间质转化(EMT)。体内研究表明,肿瘤生长抑制在治疗组中比在PTX单独组和未治疗对照组中更显著。
结论：我们的研究表明，与紫杉醇（PTX）联合使用WS或AR植物水醇提取物比单独使用PTX具有更好的敏感性和疗效。如在体外BC细胞和具有BC细胞移植物的小鼠模型中所证明的。因此，安排WS或AR单独或与PTX联合的辅助治疗对于三阴性BC(TNBC)的管理可能是有利的.需要在人类临床病症中进行进一步的研究以确定这些治疗的功效。
