共轭亚油酸通过诱导Bcl-2降低,增强低剂量顺铂在A549细胞中的凋亡效应。
Conjugated Linoleic Acid strengthens the apoptotic effect of low-dose cisplatin in A549 cells by inducing Bcl-2 downregulation.
发表日期:2023 Mar 29
作者:
Melek Yüce, Çağrı Gümüşkaptan, Ahmet Hilmi Çon, Fehmi Yazici
来源:
Stem Cell Research & Therapy
摘要:
化疗药物中广泛用于非小细胞肺癌治疗的一种是顺铂。然而,癌细胞对顺铂的耐药以及顺铂的严重副作用限制了其使用。共轭亚油酸(CLA)已被证明能够抑制体外和体内研究中的肿瘤发生,并在许多癌症中具有抗肿瘤活性。该研究旨在调查使用顺铂和CLA的潜在效果,以增加其在低剂量使用的疗效,作为非小细胞肺癌的一线治疗。进行MTT细胞毒性实验,以确定CLA与顺铂联合对非小细胞肺癌细胞株的细胞存活率的影响。采用流式细胞术确定此组合对非小细胞肺癌细胞株的凋亡效应和细胞周期分布。同时,通过实时PCR确定细胞凋亡和细胞周期相关基因表达水平。将低剂量顺铂与CLA的组合治疗导致细胞存活率显著降低,比单独使用顺铂还要好,并且观察到凋亡细胞比例增加。虽然顺铂能引起癌细胞的G1期阻滞,但是与CLA联合应用后,S期和G2期细胞百分比均有所增加。在高剂量顺铂给药中,观察到相对于耐药性化疗药物的抗凋亡蛋白Bcl-2表达减少,低剂量顺铂给药的效率降低。高剂量顺铂与CLA的联合给药显著影响了Bcl-2表达减少的恢复。版权所有 © 2023 Elsevier Inc. 发布。
One of the chemotherapeutic agents widely used in the treatment of non-small cell lung cancer (NSCLC) is cisplatin. However, the resistance of cancer cells to cisplatin and additionally serious side effects from cisplatin limit its use. Conjugated linoleic acid (CLA) has been shown to suppress the development of carcinogenesis in vitro and in vivo studies and has antitumoral activity in many cancers. The study aimed to investigate the potential effect of using cisplatin, the first-line treatment for NSCLC, in combination with CLA to increase its efficacy in low-dose use. MTT cytotoxicity assay was performed to determine the effects of CLA in combination with cisplatin on cell viability of NSCLC cell lines. The apoptotic effect of this combination on NSCLC cell lines and cell cycle distribution was determined by flow cytometry. At the same time, apoptosis and cell cycle-related gene expression levels were determined by Real-Time PCR. Combination treatment of low-dose cisplatin with CLA resulted in a significant decrease in cell viability compared to cisplatin alone, and an increase in the rate of apoptotic cells was observed. While cisplatin caused G1 phase arrest in cancer cells, there was an increase in cell percentages in S and G2 phases after combined application with CLA. In high-dose cisplatin administration, it was observed that the efficiency of the decrease in anti-apoptotic Bcl-2 expression related to resistance to chemotherapeutic agents was less than that of low-dose cisplatin administration. Combined administration of high-dose cisplatin with CLA significantly affected the recovery of Bcl-2 reduction.Copyright © 2023. Published by Elsevier Inc.