Student Research Committee, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Cell Commun Signal. 2024 Jan 2;22(1):10. doi: 10.1186/s12964-023-01446-0.
Breast cancer remains a primary global health concern due to its limited treatment options, frequent disease recurrence, and high rates of morbidity and mortality. Thereby, there is a need for more effective treatment approaches. The proposal suggests that the combination of targeted therapy with other antitumoral agents could potentially address drug resistance. In this study, we examined the antitumoral effect of combining metformin, an antidiabetic drug, with targeted therapies, including tamoxifen for estrogen receptor-positive (MCF-7), trastuzumab for HER2-positive (SKBR-3), and antibody against ROR1 receptor for triple-negative breast cancer (MDA-MB-231).
Once the expression of relevant receptors on each cell line was confirmed and appropriate drug concentrations were selected through cytotoxicity assays, the antitumor effects of both monotherapy and combination therapy on colony formation, migration, invasion were assessed in in vitro as well as tumor area and metastatic potential in ex ovo Chick chorioallantoic membrane (CAM) models.
The results exhibited the enhanced effects of tamoxifen when combined with targeted therapy. This combination effectively inhibited cell growth, colony formation, migration, and invasion in vitro. Additionally, it significantly reduced tumor size and metastatic potential in an ex ovo CAM model.
The findings indicate that a favorable strategy to enhance the efficacy of breast cancer treatment would be to combine metformin with targeted therapies.
由于治疗选择有限、疾病频繁复发以及高发病率和死亡率,乳腺癌仍然是一个主要的全球健康关注点。因此,需要更有效的治疗方法。该提案建议将靶向治疗与其他抗肿瘤药物联合使用,可能会解决耐药问题。在这项研究中,我们研究了将二甲双胍(一种抗糖尿病药物)与靶向治疗(包括用于雌激素受体阳性(MCF-7)的他莫昔芬、用于 HER2 阳性(SKBR-3)的曲妥珠单抗和用于三阴性乳腺癌(MDA-MB-231)的 ROR1 受体抗体)联合使用的抗肿瘤效果。
在通过细胞毒性测定法确认每个细胞系上相关受体的表达并选择适当的药物浓度后,在体外评估了单独用药和联合用药对集落形成、迁移和侵袭的抗肿瘤作用,以及在鸡胚绒毛尿囊膜(CAM)模型中的肿瘤面积和转移潜力。
结果表明,与靶向治疗联合使用时,他莫昔芬的效果增强。这种联合治疗在体外有效抑制了细胞生长、集落形成、迁移和侵袭。此外,它在鸡胚绒毛尿囊膜模型中显著降低了肿瘤大小和转移潜力。
这些发现表明,将二甲双胍与靶向治疗联合使用可能是增强乳腺癌治疗效果的一种有利策略。