PMID- 29978739 OWN - NLM STAT- MEDLINE DCOM- 20190424 LR - 20190424 IS - 1552-695X (Electronic) IS - 1534-7354 (Print) IS - 1534-7354 (Linking) VI - 17 IP - 4 DP - 2018 Dec TI - Antitumor Efficacy of Huqizhengxiao (HQZX) Decoction Based on Inhibition of Telomerase Activity in Nude Mice of Hepatocarcinoma Xenograft. PG - 1216-1224 LID - 10.1177/1534735418785999 [doi] AB - OBJECTIVE: Huqizhengxiao (HQZX) decoction is a mixture of traditional Chinese medicines comprising 10 herbs, with inhibitory effects on hepatocarcinoma. The aim of the study is to observe the antitumor efficacy and mechanism of HQZX decoction in nude mice with hepatocellular carcinoma xenografts. METHODS: HepG2-luc subcutaneous hepatocarcinoma was established in nude mice. The mice were divided into 5 groups: control, cinobufagin, HQZXS, HQZXM, and HQZXH with doses 13.52, 27.03, and 54.06 g/kg, respectively. HQZX decoction was prepared for intraperitoneal intragastric administration for 3 weeks. Tumor growth was measured with Vernier calipers and in vivo imaging system. alpha-Fetoprotein (AFP) was determined by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) was measured with enzyme-linked immunosorbent assay (ELISA) assay. Telomerase activity was measured with polymerase chain reaction-ELISA. Nuclear mitosis and necrosis were observed with hematoxylin-eosin stain. Apoptotic proteins of caspase-3, Bcl-2, and Bax were examined by Western blot. Signaling molecules of ERK, mTOR, and STAT3 were measured with Luminex assay. RESULTS: HQZX decoction showed good inhibition of HepG2-luc xenografts. Compared with control group, the relative tumor proliferation rate was less than 60% in the HQZXH and HQZXS. The tumor inhibition rate of HQZXH group reached 52% +/- 15%. Relative average optical density values of the HQZXS and HQZXH groups decreased significantly. The mitotic index in HQZXS, HQZXM, and HQZXH groups decreased greatly. Telomerase activity of HQZXS was clearly reduced, and, the caspase-3 expression upregulated in HQZXH group. Bcl-2 expression was downregulated in HQZXS and HQZXH. The ratios of p-ERK/ERK and p-STAT3/STAT3 in HQZXS group were significantly downregulated. CONCLUSION: HQZX decoction can clearly inhibit the growth of hepatocellular carcinoma and induce tumor apoptosis. Its antitumor mechanism may be related to reducing telomerase activity and regulating the STAT3 and ERK signal pathway. FAU - Yu, XiaoXiao AU - Yu X AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. FAU - Lin, Xue-Jun AU - Lin XJ AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. FAU - Wang, Shuang AU - Wang S AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. FAU - Liu, XiuHong AU - Liu X AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. AD - 2 Beijing Institute of Hepatology, Beijing, People's Republic of China. FAU - Li, WeiHua AU - Li W AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. AD - 2 Beijing Institute of Hepatology, Beijing, People's Republic of China. FAU - Kou, Bu-Xin AU - Kou BX AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. AD - 2 Beijing Institute of Hepatology, Beijing, People's Republic of China. FAU - Chai, MengYin AU - Chai M AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. AD - 2 Beijing Institute of Hepatology, Beijing, People's Republic of China. FAU - Chen, DeXi AU - Chen D AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. AD - 2 Beijing Institute of Hepatology, Beijing, People's Republic of China. FAU - Liu, XiaoNi AU - Liu X AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. AD - 2 Beijing Institute of Hepatology, Beijing, People's Republic of China. FAU - Wang, XiaoJun AU - Wang X AD - 1 Beijing You-An Hospital, Capital Medical University, Beijing, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180706 PL - United States TA - Integr Cancer Ther JT - Integrative cancer therapies JID - 101128834 RN - 0 (Antineoplastic Agents) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Fetal Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Animals MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/drug effects MH - Apoptosis Regulatory Proteins/metabolism MH - Carcinoma, Hepatocellular/*drug therapy/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Down-Regulation/drug effects MH - Drugs, Chinese Herbal/*pharmacology MH - Fetal Proteins/metabolism MH - Gene Expression Regulation, Neoplastic/drug effects MH - Hep G2 Cells MH - Heterografts/drug effects/metabolism MH - Humans MH - Liver Neoplasms/*drug therapy/metabolism MH - Male MH - Medicine, Chinese Traditional MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Signal Transduction/drug effects MH - Telomerase/*antagonists & inhibitors MH - Tumor Necrosis Factor-alpha/metabolism MH - Up-Regulation/drug effects MH - Xenograft Model Antitumor Assays/methods PMC - PMC6247564 OTO - NOTNLM OT - Chinese herb OT - ERK OT - STAT3 OT - apoptosis OT - hepatocarcinoma OT - telomerase activity COIS- Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2018/07/07 06:00 MHDA- 2019/04/25 06:00 PMCR- 2018/07/06 CRDT- 2018/07/07 06:00 PHST- 2018/07/07 06:00 [pubmed] PHST- 2019/04/25 06:00 [medline] PHST- 2018/07/07 06:00 [entrez] PHST- 2018/07/06 00:00 [pmc-release] AID - 10.1177_1534735418785999 [pii] AID - 10.1177/1534735418785999 [doi] PST - ppublish SO - Integr Cancer Ther. 2018 Dec;17(4):1216-1224. doi: 10.1177/1534735418785999. Epub 2018 Jul 6.