Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Ciudad de México, México.
UMAE, Hospital de Especialidades Nο. 25, Instituto Mexicano del Seguro Social, Monterrey Nuevo León, México.
In Vivo. 2024 Nov-Dec;38(6):2688-2695. doi: 10.21873/invivo.13746.
BACKGROUND/AIM: Non-small-cell lung cancer (NSCLC) is the most frequently diagnosed malignancy and the first cause of cancer-related death. Thus, finding alternative therapeutic options is crucial. Drug repurposing offers therapeutic options in a simplified and affordable manner, especially to cancer patients in developing countries. Several drugs including antihistamines and beta-adrenergic receptor blockers (beta-blockers) display antiproliferative properties on cancer cells. Interestingly, NSCLC patients who had used either antihistamines or beta-blockers showed improved response to chemotherapy or reduced mortality in comparison to non-users of any of these drugs. However, combination therapy is gaining substantial interest in many cancers including non-EGFR mutated NSCLC. Here, we investigated the antineoplastic effect of the combination of the antihistamine loratadine, the beta-blocker nebivolol, and the tyrosine-kinase inhibitor gefitinib on NSCLC cell lines.
A-549 and NCI-H1975 cell lines were used. The effect of nebivolol, gefitinib, and loratadine on the metabolic activity was studied using the MTT assay. The inhibitory concentrations (IC and IC) were calculated and used in the drug-combination experiments. Apoptosis was investigated using flow cytometry; and cell survival using the colony formation assay.
The combination nebivolol-loratadine-gefitinib produced a significant synergistic effect on inhibiting the metabolic activity and colony formation, as well as on promoting apoptosis in both cell lines. Noteworthy, the effect on the cell line carrying the EGFR mutation (NCI-H1975) was very similar to the cell line that does not exhibit such mutation (A-549 cells).
The nebivolol-gefitinib-loratadine combination may be a promising alternative for lung cancer treatment.
背景/目的：非小细胞肺癌（NSCLC）是最常见的恶性肿瘤，也是癌症相关死亡的首要原因。因此，寻找替代治疗方案至关重要。药物再利用以简化和负担得起的方式提供治疗选择，特别是对发展中国家的癌症患者。包括抗组胺药和β-肾上腺素能受体阻滞剂（β-阻滞剂）在内的几种药物对癌细胞具有抗增殖作用。有趣的是，与未使用任何这些药物的患者相比，使用过抗组胺药或β-阻滞剂的 NSCLC 患者对化疗的反应更好或死亡率降低。然而，联合治疗在包括非 EGFR 突变 NSCLC 在内的许多癌症中引起了广泛关注。在这里，我们研究了抗组胺药氯雷他定、β-阻滞剂比索洛尔和酪氨酸激酶抑制剂吉非替尼联合对 NSCLC 细胞系的抗肿瘤作用。
使用 A-549 和 NCI-H1975 细胞系。使用 MTT 测定法研究了比索洛尔、吉非替尼和氯雷他定对代谢活性的影响。计算了抑制浓度（IC 和 IC），并将其用于药物组合实验。通过流式细胞术研究细胞凋亡；通过集落形成实验研究细胞存活。
比索洛尔-氯雷他定-吉非替尼联合使用对抑制代谢活性和集落形成以及促进两种细胞系凋亡产生了显著的协同作用。值得注意的是，对携带 EGFR 突变的细胞系（NCI-H1975）的作用与不表现出这种突变的细胞系（A-549 细胞）非常相似。
比索洛尔-吉非替尼-氯雷他定联合用药可能是治疗肺癌的一种有前途的替代方案。
