Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India; Biochemistry, Faculty of Medicine, Ala-Too International University, Bishkek, Kyrgyzstan.
Biochemistry, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard (Hamdard University), New Delhi, India.
J Cancer Res Ther. 2023 Apr;19(Supplement):S0. doi: 10.4103/jcrt.jcrt_816_21.
Non-small cell lung cancer (NSCLC) is one of the aggressive tumors mostly diagnosed in the advanced stage. Therapeutic failure and drug resistance pose a major problem in NSCLC treatment primarily due to alterations in autophagy and loss of apoptosis. Therefore, the present study aimed to investigate the importance of the second mitochondria-derived activator of caspase mimetic BV6 and autophagy inhibitor chloroquine (CQ) on the regulation of apoptosis and autophagy, respectively.
Study was conducted on NCI-H23 and NCI-H522 cell lines to evaluate the effect of BV6 and CQ on the transcription and translation level of LC3-II, caspase-3, and caspase-9 genes by quantitative real-time-polymerase chain reaction and western blotting techniques.
In NCI-H23 cell line, BV6 and CQ treatments showed increased mRNA and protein expression of caspase-3, and caspase-9 compared to its untreated counterpart. BV6 and CQ treatments also caused downregulation of LC3-II protein expression compared to its counterpart. In NCI-H522 cell line, BV6 treatment showed a significantly increased expression of caspase-3 and caspase-9 mRNA and protein expression levels whereas BV6 treatment downregulated the expression level of LC3-II protein. A similar pattern was also observed in CQ treatment when compared with the respective controls. Both BV6 and CQ modulated in vitro expression of caspases and LC3-II which have critical regulatory roles in apoptosis and autophagy, respectively.
Our findings suggest that BV6 and CQ could be promising candidates in NSCLC treatment and there is a need to explore them in vivo and in clinical applications.
非小细胞肺癌（NSCLC）是一种侵袭性肿瘤，大多数在晚期诊断。治疗失败和耐药性是 NSCLC 治疗中的主要问题，主要是由于自噬改变和凋亡丧失。因此，本研究旨在探讨第二线粒体衍生的胱天蛋白酶激活剂模拟物 BV6 和自噬抑制剂氯喹（CQ）分别对凋亡和自噬的调节的重要性。
在 NCI-H23 和 NCI-H522 细胞系上进行研究，以通过定量实时聚合酶链反应和 Western 印迹技术评估 BV6 和 CQ 对 LC3-II、caspase-3 和 caspase-9 基因的转录和翻译水平的影响。
在 NCI-H23 细胞系中，BV6 和 CQ 处理与未处理的对照组相比，显示 caspase-3 和 caspase-9 的 mRNA 和蛋白表达增加。BV6 和 CQ 处理还导致 LC3-II 蛋白表达下调。在 NCI-H522 细胞系中，BV6 处理显示 caspase-3 和 caspase-9 的 mRNA 和蛋白表达水平显著增加，而 BV6 处理下调了 LC3-II 蛋白的表达水平。CQ 处理与相应的对照组相比也观察到类似的模式。BV6 和 CQ 分别调节体外 caspase 和 LC3-II 的表达，它们在凋亡和自噬中分别具有关键的调节作用。
我们的研究结果表明，BV6 和 CQ 可能是 NSCLC 治疗的有前途的候选药物，有必要在体内和临床应用中进一步研究它们。
