Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Mol Med Rep. 2024 May;29(5). doi: 10.3892/mmr.2024.13200. Epub 2024 Mar 15.
Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent and aggressive form of pancreatic cancer. Gemcitabine (GEM), the first‑line treatment for PDAC, which alleviates symptoms and enhances the quality of life of patients. However, it is prone to lead to the development of drug resistance during treatment. Interferon (IFN)‑γ exhibits antitumor and immunomodulatory properties. The present study aimed to explore the impact of IFN‑γ on the viability, migration and apoptosis of GEM‑resistant pancreatic cancer cells. Firstly, a GEM‑resistant pancreatic cancer cell line, named PANC‑1/GEM, was constructed. Hematoxylin and eosin staining analyzed the cell morphology, whereas reverse transcription‑quantitative PCR (RT‑qPCR) assessed the expression levels of the drug‑resistance genes multidrug resistance‑associated protein (MRP) and breast cancer resistance protein (BCRP). The MTT assay and cell counting techniques were used to determine the appropriate concentration of IFN‑y and its effects on cell viability. The IFN‑γ‑induced apoptosis of PANC‑1/GEM cells was assessed using an Apoptosis Detection Kit, whereas the impact of IFN‑γ on the migration of these cells was evaluated using a wound‑healing assay. The MTT assay revealed a resistance index of 22.4 in the PANC‑1/GEM cell line. RT‑qPCR indicated that, compared with in wild‑type cells, the PANC‑1/GEM resistant strain exhibited lower MRP and higher BCRP mRNA expression levels. The optimal concentration of IFN‑γ for affecting PANC‑1/GEM cells was determined to be 0.3 µg/ml. At this concentration, IFN‑γ induced PANC‑1/GEM cell apoptosis, along with a notable reduction in migration. Following treatment of PANC‑1/GEM cells with IFN‑γ, MRP expression increased whereas BCRP mRNA expression decreased, indicating a reversal in their drug‑resistance gene expression. In conclusion, IFN‑γ exhibited antitumor immune properties by upregulating MRP and downregulating BCRP expression, reversing drug‑resistance gene expression, and reducing cell viability and migration, while promoting apoptosis in PANC‑1/GEM cells. IFN‑γ could potentially serve as a treatment option for patients with GEM‑resistant pancreatic cancer.
胰腺导管腺癌 (PDAC) 是最常见和最具侵袭性的胰腺癌形式。吉西他滨 (GEM) 是 PDAC 的一线治疗药物，可缓解症状并提高患者的生活质量。然而，它在治疗过程中容易导致耐药性的发展。干扰素 (IFN)-γ 具有抗肿瘤和免疫调节特性。本研究旨在探讨 IFN-γ 对 GEM 耐药胰腺癌细胞活力、迁移和凋亡的影响。首先，构建了 GEM 耐药胰腺癌细胞系，命名为 PANC-1/GEM。苏木精和伊红染色分析细胞形态，而逆转录-定量 PCR (RT-qPCR) 评估耐药基因多药耐药相关蛋白 (MRP) 和乳腺癌耐药蛋白 (BCRP) 的表达水平。MTT 测定和细胞计数技术用于确定 IFN-γ 的适当浓度及其对细胞活力的影响。使用凋亡检测试剂盒评估 IFN-γ 诱导的 PANC-1/GEM 细胞凋亡，使用划痕愈合试验评估 IFN-γ 对这些细胞迁移的影响。MTT 测定显示 PANC-1/GEM 细胞系的耐药指数为 22.4。RT-qPCR 表明，与野生型细胞相比，PANC-1/GEM 耐药株的 MRP 和 BCRP mRNA 表达水平较低。影响 PANC-1/GEM 细胞的最佳 IFN-γ 浓度确定为 0.3μg/ml。在该浓度下，IFN-γ 诱导 PANC-1/GEM 细胞凋亡，同时迁移明显减少。用 IFN-γ 处理 PANC-1/GEM 细胞后，MRP 表达增加，而 BCRP mRNA 表达减少，表明其耐药基因表达逆转。总之，IFN-γ 通过上调 MRP 和下调 BCRP 表达、逆转耐药基因表达、降低细胞活力和迁移、促进 PANC-1/GEM 细胞凋亡，发挥抗肿瘤免疫特性。IFN-γ 可能成为 GEM 耐药胰腺癌患者的治疗选择。
