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Hedyotis Diffusa Willd (HDW), a Chinese herbal medicine, has been widelyused as an adjuvant therapy against various cancers, including hepatocellularcarcinoma (HCC). However, the underlying anticancer mechanisms are yet to be elucidated.In the present study, the anticancer effects of HDW were evaluated and the efficacyand safety of HDW combined with low-dose 5-fluorouracil (5-FU) were investigated.HepG2 cells were cultured in vitro and nude mouse xenografts were establishedin vivo. The proliferation of HepG2 cells was measured using the MTT method andflow cytometry. The mRNA and protein expression levels of cyclin-dependent kinase 2(CDK2), cyclin E and E2F1 were examined using relative quantitative real-timePCR and western blot analysis, respectively. The results showed that water extractof HDW remarkably inhibited HepG2 cell proliferation in a dose-dependent mannervia arrest of HepG2 cells at the G0/G1 phase and induction of S phase delay. Thissuppression was accompanied by a great decrease of E2F1 and CDK2 mRNA expression.In addition, HDW remarkably potentiated the anticancer effect of low-dose 5-FUin the absence of overt toxicity by downregulating the mRNA and protein levelsof CDK2, cyclin E and E2F1. Our findings support the use of HDW as adjuvant therapyof chemotherapy and suggest that HDW may potentiate the efficiency of low-dose5-FU in treating HCC.

oncology reports

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