Transition of the abnormal Savda syndrome to the hepatic carcinoma shifted unfolded protein response to autophagy was partly reversed by Savda Munziq in a rat model

• Main Authors: Yi Hao, Yue Xiao, Zhihong Zhang, Hongli Zhao, Wenyan Zhou, Xia Guo, Anwei Lu, Xin Li
• Format: Article
• Language: English
• Published: Elsevier 2020-01-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Autophagy; Unfolded protein response; Abnormal Savda Munziq; hepatic carcinoma; Uighur medicine
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332219352655

Objectives: In Uighur medicine, abnormal Savda Munziq (AMSq) is an adjuvant therapy for cancer patients with abnormal Savda syndrome (ASS) who exhibit the highest degree of pathogenicity and malignancy. The aim of the study was to understand the role(s) of AMSq in cancer patients with ASS. Methods: A total of 125 rats were divided into groups: control (NC) (n = 15), ASS (n = 25), ASS with hepatic carcinoma (ASSHC) (n = 25) as well as ASSHC treated with low dose (ASSHC-L, n = 20), medium dose (ASSHC-M, n = 20) and high dose (ASSHC-H, n = 20) AMSq. Changes in the unfolded protein response (UPR) and autophagy were analyzed by RT profiler PCR array kits, which covered 84 UPR and 84 autophagy related genes. Protein expression analyses of LC3B, ATG8, GRP78 and CHOP were carried out using western blotting. Results: CHOP and GRP78 expression was enhanced in ASS and ASSHC compared to NC rats and further increased AMSq dose-dependently, indicating an UPR triggering effect of AMSq. The ratios of ATG8/LCB3II-LCB3I protein were reduced in ASSHC rats, an effect which was partly reversed by AMSq. Compared to NC rats in the ASS group, 24 UPR genes were significantly upregulated and 3 downregulated, whereas only 5 autophagy genes were significantly upregulated and 5 downregulated. Compared to NC rats in the ASSHC group, 15 UPR genes were significantly upregulated and 10 downregulated, whereas 16 autophagy genes were significantly upregulated and 8 downregulated. The RT profiler data indicated a shift from UPR in the ASS to the autophagy response in ASSHC rats. ASMq effects on ASSHC rats comprised significant downregulation of 10 autophagy and 2 UPR genes. Conclusion: The transformation into hepatic cancer cells included a shift from endoplasmic reticulum stress-related UPR to autophagy gene activation, an effect which could be partly reversed by ASMq.