研究动态
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Doxazosin通过调节抗氧化和凋亡通路,在人类口腔癌细胞上发挥抗细胞增殖作用的机制。

Anti-cell Proliferative Mechanism of Doxazosin on Human Oral Cancer Cells Through the Modulation of Antioxidant and Apoptotic Pathway.

发表日期:2023 Mar 21
作者: Dayuan Xing, Li Li, Di Meng, Yanhui Zhang, Feng Ma
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

口腔鳞状细胞癌(OSCC)是一种具有全球性威胁的疾病,主要发生在中年和老年男性人群中。尽管不知道OSCC的确切原因,但吸食任何形式的烟草已被报道为大多数OSCC患者的原因之一。 OSCC是一种广泛侵袭性的癌症,很容易扩散到远处的器官。因此,在适当的时间治疗它是必要的,而OSCC的发病率也在不断增加。目前,化疗放疗是唯一的OSCC患者治疗方案,但会产生各种副作用。因此,具有较小副作用的治疗方法备受关注。多沙唑嗪(α1肾上腺受体拮抗剂)已被证明对前列腺、肾脏、肝脏和卵巢癌具有抗癌效果,但其在口腔癌细胞中的作用尚不明确。因此,我们通过诱导凋亡和抗氧化作用评估了多沙唑嗪对口腔鳞状癌细胞的抗癌作用。通过MTT实验分析了多沙唑嗪对正常Vero细胞和口腔癌KB细胞的细胞保护作用和抗癌作用。通过FRAP、DPPH、chemilumiscence和ORAC实验分析多沙唑嗪的抗氧化活性,TBARS、SOD和谷胱甘肽水平也被评估,并进行DCFH-DA、Rhodamine 123和AO/EtBr染色等凋亡检测技术。通过ELISA方法估计多沙唑嗪处理的KB人口腔癌细胞中凋亡蛋白的水平来确认凋亡。我们的研究结果表明,多沙唑嗪具有强大的抗氧化能力,并且它通过改变各种下游信号分子显著地诱导人类口腔癌凋亡,这在结果中得到了体现。我们的研究证明,多沙唑嗪是一种强大的抗癌药物,如果进行进一步的人类临床试验,可以用于口腔癌的治疗。 © 2023版权所有。作者独家许可Springer Science+Business Media,LLC,为Springer Nature的部分内容。
Oral squamous cell carcinoma (OSCC), a global threatening disease, is reported mostly in the middle and elderly male population. Even though the exact cause of OSCC was not known, consumption of tobacco in any form has been reported in most of OSCC patients. OSCC is a massive invasive type of cancer which easily spreads to the distant organs. Hence treating it at appropriate time is necessary and the rate of OSCC incidence is also constantly increasing. At present, chemoradiation is the only therapy prescribed for OSCC patients which renders various side effects. Hence, the treatment with lesser side effect was of current research interest. Doxazosin (α1 adrenorecptor antagonist) had been proven to render anticancer effect in prostate, renal, hepatic, and ovarian cancers but its role in oral cancer cells was not been elucidated. Therefore, we have assessed the anticancer effect of doxazosin on oral squamous cancer cells via through the induction of apoptosis, and antioxidant property. The cytoprotective effect of doxazosin on normal Vero cells and anticancer effect on oral cancer KB cells were analyzed with MTT assay. Doxazosin antioxidant activity were analyzed by their reactivity with free radicals and metal ions by the method of FRAP, DPPH, chemilumiscence, and ORAC assay. The antioxidant levels were also assessed by TBARS, SOD, and glutathione levels, and later on apoptosis staining techniques like DCFH-DA, Rhodamine 123, and AO/EtBr stain were conducted. Apoptosis was confirmed by estimating the levels of apoptotic proteins in doxazosin-treated KB human oral cancer cells by ELISA method. The results from our study show that doxazosin is a potent antioxidant and it significantly induces apoptosis in human oral cancer by altering various cellular molecules at downstream signaling which has been depict in the results. Our study proves doxazosin as a potent anticancer drug which may be used in the treatment of oral carcinoma, if it is subjected to further research using human clinical trials.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.