Vatankhah Mohammad Amin, Ziyabakhsh Alireza, Vakili Ojarood Mohammad
Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Radiology, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Pharm Res. 2024 Nov 16;23(1):e153408. doi: 10.5812/ijpr-153408. eCollection 2024 Jan-Dec.
Chemotherapy remains a primary approach to cancer treatment, widely applied in bladder cancer (BC). However, the various side effects and resistance associated with chemotherapeutic drugs pose significant challenges in BC therapy, prompting interest in natural compounds like luteolin. Studies focus on its effects on key biological processes involved in BC, including metastasis, apoptosis, and autophagy.
This study investigated the regulation of mRNA expression of genes associated with apoptosis (BCL2, P53), autophagy (ULK1, ATG12), and metastasis (MMP2, MMP9) in malignant BC cells treated with luteolin.
This was an in vitro experimental study. EJ138 BC cells were treated with various concentrations of luteolin, and its impact on cell viability, proliferation, and gene expression was assessed.The cytotoxic effect of luteolin on EJ138 BC cells was evaluated using the MTT assay after 24- and 48-hour treatments with different luteolin concentrations. Flow cytometry was performed to examine luteolin's anti-proliferative effect, and RT-PCR was used to analyze mRNA expression of BCL2, P53, ULK1, ATG12, MMP2, and MMP9 genes.
MTT assay results confirmed that luteolin reduced the proliferation rate of BC cells. Flow cytometry indicated increased cell death in EJ138 BC cells following luteolin treatment. RT-PCR findings demonstrated that luteolin upregulated P53, ULK1, and ATG12 expression while downregulating BCL2 mRNA expression. However, luteolin treatment in EJ138 cells did not significantly alter MMP2 and MMP9 expression levels.
These findings indicate that luteolin exerts cytotoxic effects on EJ138 BC cells by dysregulating mRNA expression of genes involved in apoptosis and autophagy. Therefore, luteolin shows potential as an effective anti-cancer agent for BC therapy.
化疗仍然是癌症治疗的主要方法，广泛应用于膀胱癌（BC）。然而，化疗药物的各种副作用和耐药性给膀胱癌治疗带来了重大挑战，这促使人们对木犀草素等天然化合物产生兴趣。研究聚焦于其对膀胱癌关键生物学过程的影响，包括转移、凋亡和自噬。
本研究调查了木犀草素处理的恶性膀胱癌细胞中与凋亡（BCL2、P53）、自噬（ULK1、ATG12）和转移（MMP2、MMP9）相关基因的mRNA表达调控情况。
这是一项体外实验研究。用不同浓度的木犀草素处理EJ138膀胱癌细胞，并评估其对细胞活力、增殖和基因表达的影响。用不同浓度木犀草素处理24小时和48小时后，采用MTT法评估木犀草素对EJ138膀胱癌细胞的细胞毒性作用。进行流式细胞术以检测木犀草素的抗增殖作用，并使用RT-PCR分析BCL2、P53、ULK1、ATG12、MMP2和MMP9基因的mRNA表达。
MTT分析结果证实木犀草素降低了膀胱癌细胞的增殖率。流式细胞术表明木犀草素处理后EJ138膀胱癌细胞的细胞死亡增加。RT-PCR结果表明，木犀草素上调了P53、ULK1和ATG12的表达，同时下调了BCL2 mRNA的表达。然而，木犀草素处理EJ138细胞并未显著改变MMP2和MMP9的表达水平。
这些发现表明，木犀草素通过失调参与凋亡和自噬的基因的mRNA表达，对EJ138膀胱癌细胞发挥细胞毒性作用。因此，木犀草素显示出作为膀胱癌治疗有效抗癌药物的潜力。
