Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran AND Department of Immunology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Department of Immunology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Iran J Allergy Asthma Immunol. 2020 Aug 25;19(4):426-436. doi: 10.18502/ijaai.v19i4.4117.
Several studies have been conducted to find suitable combinations of drugs to increase the efficacy of chemotherapy and reduce the resistance of tumor cells to treatment. Lipopolysaccharide (LPS), as a ligand for Toll-like receptor 4 (TLR-4), can modify immune responses in different cancers. Although multiple studies have been performed in this area, the effect of LPS on tumor cells remains controversial. In the present study, the cytotoxic effects of 5-fluorouracil (5-FU), with or without LPS, were evaluated in human breast cancer cell line (MCF-7) on apoptosis and gene expression in downstream signaling pathways. MCF-7 was obtained from the Pasteur Institute of Iran. The effects of LPS and 5-FU on cytotoxicity, apoptosis, and gene expression in NF-κB, ERK, and AKT signaling pathways were evaluated by MTT assay, Annexin V/propidium iodide (PI) apoptosis assay, and qRT-PCR, respectively. Our findings showed that LPS alone did not significantly affect cytotoxicity or apoptosis, compared to the control cells (untreated cells), while combined with 5-FU, it caused a significant increase in the apoptosis of cancer cells and decreased cell viability. It was also concluded that LPS in combination with 5-FU increased TLR-4 expression and down-regulated gene expression in NF-κB, ERK, and AKT pathways (p=0.001). Although the role of LPS in tumor inhibition or progression remains controversial, our findings suggest that LPS can be considered a novel complementary approach intranslational oncology research of breast cancer therapy.
已经进行了多项研究，以寻找合适的药物组合，以提高化疗的疗效并降低肿瘤细胞对治疗的耐药性。脂多糖（LPS）作为 Toll 样受体 4（TLR-4）的配体，可以修饰不同癌症中的免疫反应。尽管在这一领域进行了多项研究，但 LPS 对肿瘤细胞的影响仍存在争议。在本研究中，评估了 LPS 与 5-氟尿嘧啶（5-FU）联合应用对人乳腺癌细胞系（MCF-7）的细胞毒性作用及其对下游信号通路中凋亡和基因表达的影响。MCF-7 细胞系购自伊朗巴斯德研究所。通过 MTT 测定法、Annexin V/碘化丙啶（PI）凋亡测定法和 qRT-PCR 分别评估 LPS 和 5-FU 对 NF-κB、ERK 和 AKT 信号通路中的细胞毒性、凋亡和基因表达的影响。我们的研究结果表明，与对照细胞（未处理细胞）相比，LPS 单独作用时对细胞毒性或凋亡没有显著影响，而与 5-FU 联合使用时，会导致癌细胞凋亡显著增加，细胞活力降低。此外，还得出结论，LPS 与 5-FU 联合使用会增加 TLR-4 的表达，并下调 NF-κB、ERK 和 AKT 通路中的基因表达（p=0.001）。尽管 LPS 在肿瘤抑制或进展中的作用仍存在争议，但我们的研究结果表明，LPS 可以被认为是乳腺癌治疗转化肿瘤学研究中的一种新的互补方法。
