Saber Sameh, Mahmoud Amr, Helal Noha, El-Ahwany Eman, Abdelghany Rasha
Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.
Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Open Access Maced J Med Sci. 2018 Jun 6;6(6):955-960. doi: 10.3889/oamjms.2018.167. eCollection 2018 Jun 20.
Preclinical studies have demonstrated that renin-angiotensin system (RAS) signalling has strong tumour-promoting effects and RAS inhibition was associated with improvement in the overall survival in some cancer types including hepatocellular carcinoma (HCC).
We aimed to investigate the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) on the survival of mice with diethylnitrosamine (DEN) induced HCC.
HCC was induced by weekly i.p. administration of DEN. Mice were treated with sorafenib (SO) (30 mg/kg), perindopril (PE) (1 mg/kg), fosinopril (FO) (2 mg/kg), losartan (LO) (10 mg/kg), PE (1 mg/kg) + SO (30 mg/kg), FO (2 mg/kg) + SO (30 mg/kg), or LO (10 mg/kg) + SO (30 mg/kg). Survival analysis was done using the Kaplan-Meier method, and the log-rank test was used for assessing the significance of difference between groups.
The administration of PE, FO and LO as monotherapy or as combined with SO resulted in marked improvement in the liver histologic picture with no impact on overall survival of mice.
Interfering the RAS either through the inhibition of ACE or the blockade of angiotensin II type 1 (AT1) receptors has similar effects on the liver of DEN-induced HCC mice and is not associated with longer survival due to detrimental effects of DEN on other organs. Hence, repetitive administration of DEN in such models of HCC is not suitable for mortality assessment studies.
临床前研究表明，肾素 - 血管紧张素系统（RAS）信号传导具有强大的肿瘤促进作用，RAS抑制与包括肝细胞癌（HCC）在内的某些癌症类型的总生存期改善相关。
我们旨在研究血管紧张素转换酶抑制剂（ACEIs）或血管紧张素II受体阻滞剂（ARBs）对二乙基亚硝胺（DEN）诱导的HCC小鼠生存的影响。
通过每周腹腔注射DEN诱导HCC。小鼠分别接受索拉非尼（SO）（30 mg/kg）、培哚普利（PE）（1 mg/kg）、福辛普利（FO）（2 mg/kg）、氯沙坦（LO）（10 mg/kg）、PE（1 mg/kg）+ SO（30 mg/kg）、FO（2 mg/kg）+ SO（30 mg/kg）或LO（10 mg/kg）+ SO（30 mg/kg）治疗。使用Kaplan-Meier方法进行生存分析，并使用对数秩检验评估组间差异的显著性。
PE、FO和LO作为单一疗法或与SO联合使用可显著改善肝脏组织学图像，但对小鼠的总生存期无影响。
通过抑制ACE或阻断血管紧张素II 1型（AT1）受体干扰RAS对DEN诱导的HCC小鼠肝脏具有相似的作用，并且由于DEN对其他器官的有害作用，与更长的生存期无关。因此，在这种HCC模型中重复给予DEN不适合进行死亡率评估研究。
