i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
Cancer Drug Resistance Group, IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
Int J Mol Sci. 2022 Mar 26;23(7):3631. doi: 10.3390/ijms23073631.
Pirfenidone, an antifibrotic drug, has antitumor potential against different types of cancers. Our work explored whether pirfenidone sensitizes non-small cell lung cancer (NSCLC) cell lines to chemotherapeutic treatments. The cytotoxic effect of paclitaxel in combination with pirfenidone against three NSCLC cell lines (A549, NCI-H322 and NCI-H460) was evaluated using the sulforhodamine B assay. The effects of this combination on cell viability (trypan blue exclusion assay), proliferation (BrdU incorporation assay), cell cycle (flow cytometry following PI staining) and cell death (Annexin V-FITC detection assay and Western blot) were analyzed on the most sensitive cell line (NCI-H460). The cytotoxic effect of this drug combination was also evaluated against two non-tumorigenic cell lines (MCF-10A and MCF-12A). Finally, the ability of pirfenidone to sensitize NCI-H460 cells to a combination of paclitaxel plus carboplatin was assessed. The results demonstrated that pirfenidone sensitized NCI-H460 cells to paclitaxel treatment, reducing cell growth, viability and proliferation, inducing alterations in the cell cycle profile and causing an increase in the % of cell death. Remarkably, this combination did not increase cytotoxicity in non-tumorigenic cells. Importantly, pirfenidone also sensitized NCI-H460 cells to paclitaxel plus carboplatin. This work highlights the possibility of repurposing pirfenidone in combination with chemotherapy for the treatment of NSCLC.
吡非尼酮是一种抗纤维化药物，具有针对多种癌症的抗肿瘤潜力。我们的工作探讨了吡非尼酮是否能使非小细胞肺癌（NSCLC）细胞系对化疗药物更敏感。采用磺酰罗丹明 B 测定法评估紫杉醇联合吡非尼酮对三种 NSCLC 细胞系（A549、NCI-H322 和 NCI-H460）的细胞毒性作用。采用台盼蓝排斥试验、BrdU 掺入试验、PI 染色后流式细胞术检测细胞周期、Annexin V-FITC 检测和 Western blot 分析该联合用药对最敏感细胞系（NCI-H460）的细胞活力、增殖、细胞死亡的影响。还评估了该药物组合对两种非致瘤细胞系（MCF-10A 和 MCF-12A）的细胞毒性作用。最后，评估了吡非尼酮使 NCI-H460 细胞对紫杉醇加卡铂联合用药敏感的能力。结果表明，吡非尼酮使 NCI-H460 细胞对紫杉醇治疗更敏感，降低细胞生长、活力和增殖，诱导细胞周期谱改变，并导致细胞死亡百分比增加。值得注意的是，该联合用药并未增加非致瘤细胞的细胞毒性。重要的是，吡非尼酮还使 NCI-H460 细胞对紫杉醇加卡铂敏感。这项工作强调了将吡非尼酮与化疗联合用于治疗 NSCLC 的可能性。
