Department of Biochemistry, Faculty of Veterinary Medicine, Benha University, Egypt.
Health Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
Asian Pac J Cancer Prev. 2020 Jun 1;21(6):1709-1716. doi: 10.31557/APJCP.2020.21.6.1709.
Combination therapy has been the trendy of care, particularly in cancer remedy, since it is a rational approach to increase response and tolerability and to diminish resistance. Hence, there is a growing interest in combining anticancer drugs to maximizing efficacy with minimum systemic toxicity through the delivery of lower drug doses. Therefore, in the present study, the value of combination between benzethonium chloride (benzo) and endoxan (endo) as anti-tumor drug sensitization of hepatocellular carcinoma HCC treatment were detected both in vitro and in vivo. Crystal violet test was performed to detect the proliferation of HepG2 cells treated with benzo or/and endo. In addition, the HCC rat model was established by diethylnitrosamine (DEN) administration. The antitumor effect was enhanced with the combined treatment of the two drugs, particularly in the group with benzo and endo. The results confirmed that the HCC condition was developed in response to lower expressions of caspase 3 and P53 which, in turn, was due to the overexpression of Bcl-2, and downregulation of cytochrome C. The treatment with benzo combined with endo caused significant activation of caspase-3 mediated apoptotic signals that could be responsible for its anti-HCC potential. Meantime, benzo combined with endo treatments could reduce the hepatocellular carcinogenesis by reducing the expression of MMP-9. Therefore, benzo and endo treatments may be a hopeful therapeutic drug for HCC. Also, more studies are recommended to feat the idea of this research for medical use.
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联合治疗一直是护理的趋势,特别是在癌症治疗中,因为它是一种增加反应和耐受性、减少耐药性的合理方法。因此,人们越来越感兴趣的是通过降低药物剂量来联合使用抗癌药物,以最大限度地提高疗效和最小的全身毒性。因此,在本研究中,检测了苯扎氯铵(benzo)和氮芥(endo)联合作为肝癌 HCC 治疗的抗肿瘤药物增敏剂的体内外价值。结晶紫试验用于检测用 benzo 或/和 endo 处理的 HepG2 细胞的增殖。此外,通过二乙基亚硝胺(DEN)给药建立 HCC 大鼠模型。两种药物联合治疗增强了抗肿瘤作用,尤其是在 benzo 和 endo 联合治疗组。结果证实,HCC 状况的发展是由于 caspase 3 和 P53 的表达降低,而 caspase 3 和 P53 的表达降低反过来又导致 Bcl-2 过表达和细胞色素 C 下调。benzo 与 endo 联合治疗可显著激活 caspase-3 介导的凋亡信号,这可能是其抗 HCC 潜能的原因。同时,benzo 联合 endo 治疗可通过降低 MMP-9 的表达来减少肝细胞癌的发生。因此,benzo 和 endo 治疗可能是 HCC 的一种有希望的治疗药物。此外,建议进行更多的研究来验证这一研究思路在医学上的应用。