Department of Cardiothoracic Surgery, People's Hospital of Chizhou, Chizhou, 247000, China.
Mol Biol Rep. 2024 Mar 23;51(1):435. doi: 10.1007/s11033-024-09347-2.
XIAP-associated factor 1 (XAF1) has been found to participate in the progression of multiple human cancers. Nevertheless, its role as well as the reaction mechanism in non-small cell lung cancer (NSCLC) still remains obscure.
In this study, the protein expression of XAF1 in NSCLC cell lines was evaluated using western blot. With the employment of CCK-8 assay, EdU staining, wound healing and transwell, capabilities of NSCLC cells to proliferate, migrate and invade were assessed. Cell apoptotic level and cell cycle were resolved utilizing flow cytometry. Western blot was applied for the estimation of apoptosis- and endoplasmic reticulum (ER) stress-related proteins.
It was discovered that XAF1 expression was conspicuously reduced in NSCLC cell lines. XAF1 overexpression suppressed H1299 cell proliferative, invasive and migrative capabilities, but exhibited promotive effects on cell cycle arrest. Meanwhile, XAF1 overexpression inhibited cisplatin resistance in H1299 and H1299/DDP cells by promoting cell apoptosis and enhanced the expression levels of ER stress-related proteins CHOP, GRP78 and ATF4. What's more, 4-PBA treatment reversed the impacts of XAF1 overexpression on the proliferative, invasive, migrative and apoptotic capabilities of H1299 cells, as well as cell cycle and cisplatin resistance.
In conclusion, XAF1 overexpression impeded the advancement of NSCLC and repressed cisplatin resistance of NSCLC cells through inducing ER stress, which indicated that XAF1 might be a novel targeted-therapy for NSCLC.
XIAP 相关因子 1（XAF1）已被发现参与多种人类癌症的进展。然而，其在非小细胞肺癌（NSCLC）中的作用及其反应机制仍不清楚。
在这项研究中，通过 Western blot 评估了 NSCLC 细胞系中 XAF1 的蛋白表达。利用 CCK-8 测定法、EdU 染色、划痕愈合和 Transwell 实验评估 NSCLC 细胞的增殖、迁移和侵袭能力。通过流式细胞术评估细胞凋亡水平和细胞周期。利用 Western blot 评估凋亡和内质网（ER）应激相关蛋白。
研究发现，XAF1 在 NSCLC 细胞系中的表达明显降低。XAF1 过表达抑制了 H1299 细胞的增殖、侵袭和迁移能力，但促进了细胞周期停滞。同时，XAF1 过表达通过促进细胞凋亡和增强 ER 应激相关蛋白 CHOP、GRP78 和 ATF4 的表达水平，抑制了 H1299 和 H1299/DDP 细胞对顺铂的耐药性。此外，4-PBA 处理逆转了 XAF1 过表达对 H1299 细胞增殖、侵袭、迁移和凋亡能力以及细胞周期和顺铂耐药性的影响。
总之，XAF1 过表达通过诱导 ER 应激抑制 NSCLC 的进展并抑制 NSCLC 细胞对顺铂的耐药性，表明 XAF1 可能成为 NSCLC 的一种新的靶向治疗方法。
