title: Cidan inhibits liver cancer cell growth by reducing COX-2 and VEGF expression and cell cycle arrest.
abstract: Cidan is a traditional Chinese medicine formula that has been used for >10 years as an antitumor drug. In the present study, the antitumor effect of cidan on hepatocellular carcinoma (HCC) and the underlying molecular mechanisms were investigated. A total of 372 patients with primary HCC, as confirmed by pathological examination in the Eastern Hepatobiliary Surgery Hospital and Beijing Oncology Hospital of Weida TCM, were prospectively enrolled in the study. In total, 92 patients were treated with cidan capsules for three months postoperatively, while 280 patients served as controls. The efficacy of cidan was analyzed by monitoring associated symptoms and liver function tests, including measuring the levels of α-1-fetoprotein, α-L-fucosidase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase. In addition,in vivoanalysis was performed using mice Hepa1-6 xenograft models, whilein vitrostudies were performed with SMMC-7721 and CSQT-1 cells; this included cidan-dependent cell viability and migration assays, cell cycle analyses and the evaluation of cidan effects on cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) mRNA transcription rates using quantitative polymerase chain reaction. The postoperative two-year overall survival (77 and 58% for the cidan and control groups, respectively; P<0.01) and disease-free survival (36 and 24% for the cidan and control groups, respectively; P<0.01) rates were superior in the cidan-treated group when compared with the control. In addition, the size and weight of the tumor xenografts in the C57BL/6 mice were significantly reduced in a time- and dose-dependent manner following cidan treatment (P<0.01). Cidan significantly reduced the cell viability of SMMC-7721 and CSQT-1 cells after four and five days when compared with the control (P<0.01). Furthermore, COX-2 and VEGF mRNA expression levels decreased following cidan treatment (P<0.01), and cidan treatment resulted in enhanced G1 and G2/M cell cycle arrest of CSQT-1 cells. Therefore, cidan effectively inhibited cell proliferation, reduced cell viability and downregulated COX-2 and VEGF expression levels in hepatoma cells.
authors.affiliation: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Beijing Oncology Hospital Of Weida TCM, Beijing 100023, P.R. China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Juxian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Chongde
authors.initials: C
authors.lastname: Lu
authors.affiliation: Beijing Oncology Hospital Of Weida TCM, Beijing 100023, P.R. China.
authors.forename: Weida
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Shuqun
authors.initials: S
authors.lastname: Cheng
keywords: Rhizoma Curcumae; cidan; cyclooxygenase-2; primary hepatocellular carcinoma; vascular endothelial growth factor