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
| Autor: | Xuzheng Chen, Lianming Liao, Zhi-yun Cao, Jian Du, Tuan-Sheng Chen, Zhizhen Liu, You-Quan Zhang, Yin-Tao Su |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Mice Nude Cell Growth Processes Resting Phase Cell Cycle Flow cytometry S Phase Hedyotis diffusa Mice Nude mouse Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Hedyotis Animals Humans RNA Messenger Mice Inbred BALB C biology medicine.diagnostic_test Oncogene Dose-Response Relationship Drug Cell growth Plant Extracts Cyclin-Dependent Kinase 2 Liver Neoplasms Water Drug Synergism General Medicine Hep G2 Cells Cell cycle biology.organism_classification G1 Phase Cell Cycle Checkpoints Xenograft Model Antitumor Assays Oncology Cell culture Apoptosis Cancer research Female Fluorouracil E2F1 Transcription Factor |
| Zdroj: | Oncology reports. 28(2) |
| ISSN: | 1791-2431 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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