Water extract of Hedyotis Diffusa Willd suppresses proliferation of             human HepG2 cells and potentiates the anticancer efficacy of low-dose 5-fluorouracil             by inhibiting the CDK2-E2F1 pathway.
Hedyotis Diffusa Willd (HDW), a Chinese herbal medicine, has been widely             used as an adjuvant therapy against various cancers, including hepatocellular             carcinoma (HCC). However, the underlying anticancer mechanisms are yet to be elucidated.             In the present study, the anticancer effects of HDW were evaluated and the efficacy             and safety of HDW combined with low-dose 5-fluorouracil (5-FU) were investigated.             HepG2 cells were cultured in vitro and nude mouse xenografts were established             in vivo. The proliferation of HepG2 cells was measured using the MTT method and             flow cytometry. The mRNA and protein expression levels of cyclin-dependent kinase 2             (CDK2), cyclin E and E2F1 were examined using relative quantitative real-time             PCR and western blot analysis, respectively. The results showed that water extract             of HDW remarkably inhibited HepG2 cell proliferation in a dose-dependent manner             via arrest of HepG2 cells at the G0/G1 phase and induction of S phase delay. This             suppression was accompanied by a great decrease of E2F1 and CDK2 mRNA expression.             In addition, HDW remarkably potentiated the anticancer effect of low-dose 5-FU             in the absence of overt toxicity by downregulating the mRNA and protein levels             of CDK2, cyclin E and E2F1. Our findings support the use of HDW as adjuvant therapy             of chemotherapy and suggest that HDW may potentiate the efficiency of low-dose             5-FU in treating HCC.
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, and Hospital of Fujian Agriculture and Forestry University, Fuzhou 350108, PR China.
Xu-Zheng
XZ
Chen
Zhi-Yun
ZY
Cao
Tuan-Sheng
TS
Chen
You-Quan
YQ
Zhang
Zhi-Zhen
ZZ
Liu
Yin-Tao
YT
Su
Lian-Ming
LM
Liao
Jian
J
Du
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D032064:Hedyotis / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D014867:Water / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D010936:Plant Extracts; D012333:RNA, Messenger; D014867:Water; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D005472:Fluorouracil