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诺米芬辛的电离辐射转化及其对MCF-7细胞的抗癌作用探索。

Transformation of nomifensine using ionizing radiation and exploration of its anticancer effects in MCF-7 cells.

作者信息

Kang Seong Hee, Bak Dong-Ho, Yeoup Chung Byung, Bai Hyoung-Woo

机构信息

Research Division for Radiation Science, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeollabuk 56212, Republic of Korea.

Radiation Biotechnology and Applied Radioisotope Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.

出版信息

Exp Ther Med. 2022 Apr;23(4):306. doi: 10.3892/etm.2022.11235. Epub 2022 Feb 23.

Abstract

Breast cancer is one of the most challenging diseases to treat in humans worldwide. There are several alternatives in treating this life-threatening disease; however, chemoresistance is probably the biggest obstacle to the treatment of breast cancer. It may be essential to develop a therapeutic candidate material with less reversible effects and high treatment efficiency to solve this problem. The present study applied an ionizing radiation approach employing nomifensine (NF) to transform its chemical characteristics and investigated its potential to kill human breast cancer cells (MCF-7). Irradiated (IR-) NF was analyzed using high-performance liquid chromatography. The findings showed that NF inhibited the proliferation of breast cancer cells and increased the rate of apoptosis. In addition, IR-NF induced the accumulation of cytosolic reactive oxygen species and enhanced mitochondrial aggregation. Additionally, mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH 2-terminal kinase) were involved in damage signaling induced by IR-NF and IR-NF suppressed β-catenin nuclear translocation. It is suggested that irradiation can be an effective method to maximize the efficacy of existing drugs and that IR-NF has the potential to be a drug candidate for treating patients with breast cancer.

摘要

乳腺癌是全球范围内最难治疗的人类疾病之一。治疗这种危及生命的疾病有多种选择;然而,化疗耐药性可能是乳腺癌治疗的最大障碍。开发一种具有较低可逆效应和高治疗效率的治疗候选材料可能是解决这个问题的关键。本研究采用电离辐射方法,利用诺米芬辛(NF)改变其化学特性,并研究其杀死人乳腺癌细胞(MCF-7)的潜力。使用高效液相色谱法分析辐照后的(IR-)NF。研究结果表明,NF抑制乳腺癌细胞的增殖并增加凋亡率。此外,IR-NF诱导胞质活性氧的积累并增强线粒体聚集。此外,丝裂原活化蛋白激酶(细胞外信号调节激酶1/2、p38和c-Jun NH2末端激酶)参与了IR-NF诱导的损伤信号传导,并且IR-NF抑制了β-连环蛋白的核转位。研究表明,辐射可以是一种有效提高现有药物疗效的方法,并且IR-NF有潜力成为治疗乳腺癌患者的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/150b/8931636/296de6c1691e/etm-23-04-11235-g00.jpg

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