Selvaraj Nagaraj Balan, Swaroop Akey Krishna, Mariappan Esakkimuthukumar, Natarajan Jawahar, Thangavelu Prabha, Selvaraj Jubie
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Tamilnadu, India.
Department of Pharmaceutics , JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Tamilnadu, India.
Anticancer Agents Med Chem. 2023;23(18):2056-2071. doi: 10.2174/1871520623666230822100006.
Targeted therapies, specifically ErbB family tyrosine kinase inhibitors, have demonstrated potential for improving outcomes in patients with ErbB2-positive breast cancer. Despite their effectiveness, these therapies are associated with limitations, including high costs, side effects, drug resistance, lack of specificity, and toxicity. To overcome these challenges, drug repurposing has emerged as a promising strategy in breast cancer treatment.
The aim of this investigation was to assess the influence of calcitriol on breast cancer cell lines expressing ErbB2 and comparing its effects with the conventional treatment, neratinib.
We employed an MTT test to determine cell viability and utilized staining techniques to assess cell apoptosis. Flow cytometry was used to evaluate cell cycle arrest, while a scratch wound healing test was performed to examine cancer cell migration ability. Additionally, gene expression studies were conducted for calcitriol and neratinib to support our hypothesis regarding the ErbB2 gene.
The repurposing of calcitriol demonstrated enhanced efficacy in suppressing cancer cell growth in ErbB2- positive breast cancer. Proportionally, calcitriol significantly reduced the viability of SK-BR-3 cells, similar to neratinib. Furthermore, calcitriol exhibited significant cytotoxicity against neratinib and substantially reduced breast cancer cell growth. These findings were corroborated by the wound healing assay, cell cycle arrest analysis, and gene expression studies, demonstrating comparable efficacy to the standard treatment, neratinib.
The findings from this investigation offer compelling proof that highlights the promising role of calcitriol as an adjuvant drug with antiproliferative and antitumoral effects in the management of ErbB2-positive breast carcinoma patients. Therefore, we recommend further evaluation of calcitriol in clinical settings, particularly for the treatment of ErbB2-positive breast cancer, as it shows promise as a valuable therapeutic option.
靶向治疗,特别是表皮生长因子受体(ErbB)家族酪氨酸激酶抑制剂,已显示出改善ErbB2阳性乳腺癌患者预后的潜力。尽管这些疗法有效,但它们存在局限性,包括成本高、副作用、耐药性、缺乏特异性和毒性。为了克服这些挑战,药物再利用已成为乳腺癌治疗中一种有前景的策略。
本研究的目的是评估骨化三醇对表达ErbB2的乳腺癌细胞系的影响,并将其与传统治疗药物奈拉替尼的效果进行比较。
我们采用MTT试验测定细胞活力,并利用染色技术评估细胞凋亡。使用流式细胞术评估细胞周期停滞,同时进行划痕伤口愈合试验以检测癌细胞迁移能力。此外,对骨化三醇和奈拉替尼进行基因表达研究,以支持我们关于ErbB2基因的假设。
骨化三醇的再利用在抑制ErbB2阳性乳腺癌癌细胞生长方面显示出增强的疗效。相应地,骨化三醇显著降低了SK-BR-3细胞的活力,与奈拉替尼相似。此外,骨化三醇对奈拉替尼表现出显著的细胞毒性,并大幅降低了乳腺癌细胞的生长。伤口愈合试验、细胞周期停滞分析和基因表达研究证实了这些发现,表明其疗效与标准治疗药物奈拉替尼相当。
本研究结果提供了有力证据,突出了骨化三醇作为辅助药物在ErbB2阳性乳腺癌患者管理中具有抗增殖和抗肿瘤作用的前景。因此,我们建议在临床环境中进一步评估骨化三醇,特别是用于治疗ErbB2阳性乳腺癌,因为它有望成为一种有价值的治疗选择。