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.

Abstract. Jiedu Xiaozheng Yin (JXY), a polyherbal formula of traditional Chinese medicine (TCM), has been used to treat various kinds of cancer in China. However, the mechanism of its anticancer activity has yet to be elucidated. Air-dried herbs were extracted with reagents of different polarity. HepG2 cells were treated with different doses of ethyl acetate extract (EE-JXY) and chloroform extract (CE-JXY) for 24 h. Cell viability was detected by MTT assay. Colony formation ability was also evaluated. Cell cycle was evaluated by FACS. Tumor bearing BALB/c nude mice was treated with EE-JXY (0.06 g/kg) for 20 days. Tumor volume and weight were monitored. The percentage of PCNA-positive cells and the level of G1 phase proteins [cyclin-dependent kinase2 (CDK2), cyclin-dependent kinase4 (CDK4), cyclin D and cyclin E and G2 phase proteins [cyclin-dependent kinase1 (CDK1), cyclin A and cyclin B] were detected by immunohistochemistry and western blotting.EE-JXY and CE-JXY dose-dependently inhibited the growth of HepG2 cells (P<0.01 for both). Furthermore, EE-JXY inhibited the formation of cell colonies and blocked the cell cycle to G1 phase in a dose-dependent manner (P<0.01 for all). EE-JXY showed an obviously antitumor effect in vivo (P<0.05). Further investigation showed that EE-JXY decreased the proliferation index of tumors (P<0.01) through increasing the expression of G1-related proteins (cyclin D and cyclin E, P<0.05 and P<0.01). These results suggested that JXY inhibits the growth of HepG2 cells at least via arresting the cell cycle at the G0/G1 phase. IntroductionHepatocellular carcinoma (HCC) is listed as the fifth most common malignancy in the world. Although surgical treatment and non-surgical therapeutic modalities such as chemotherapy, radiotherapy and interventional therapy have been employed, HCC is rarely curative (1,2). For this reason more and more patients and oncologists are seeking alternative medicines to improve the curative rate of HCC. Traditional Chinese medicine (TCM) has been widely used in China to treat HCC because it can improve immune function of patients and alleviate chemoradiotherapy-related side effects (3).In TCM, herbs commonly used for cancer treatment can be divided into two categories. One is nutritious and tonic herbs and the other is heat-clearing and detoxification herbs. Nutritious and tonic herbs (Fuzheng herbs) act by improving the immune function to fight cancer (such as Astragalus, Ganoderma lucidum and ginseng) (4-6). Heat clearing and detoxication herbs (Qingre Jiedu herbs) may directively kill tumor cells [such as Hedyotis diffusa Willd (HDW), Sophora flavescens (SF), Pseudobulbus Cremastrae (PC), Prunella, Bidens, banzhilian] (7-9). In TCM, cancer is considered to be caused by accumulation of foreign toxins, and cancer itself is also considered to be a toxin that is harmful to human body. The above herbs may contain ingredients that can inhibit proliferation and promote apoptosis of tumor cells. For example, we found that HDW water extract may inhibit proliferation o...

BackgroundThe Consolidated Standards for Reporting Trials (CONSORT) are aimed to standardize clinical trial reporting. Our objective is to compare the quality of randomized clinical trials (RCTs) of traditional Chinese medicine (TCM) published in 2005–2009 and 2011–2012 according to the current CONSORT statements and Jadad scale.MethodsData Sources: Reports on RCTs of TCM in the China National Knowledge Infrastructure database (CNKI database) for manuscripts published from 2005 to 2009 and 2011–2012. Search terms included TCM and clinical trial. Study Selection: Manuscripts that reported RCTs of TCM were included. Data Extraction: Independent extraction of articles was done by 3 authors. Disagreement was discussed until agreement was reached. According to the CONSORT checklist, an item was scored as 1 when the item was described in the paper. Otherwise the item was scored as 0.ResultsA total of 4133 trials in 2005–2009 and 2861 trials in 2011–2012 were identified respectively. There was a significant increase in proportion of reports that included details of background (24.71% vs 35.20%, P < 0.001), participants (49.79% vs 65.26%, P < 0.001), the methods of random sequence generation (13.77% vs 19.85%, P < 0.001), statistical methods (63.00% vs 72.77%, P < 0.001) and recruitment date (70.14% vs 80.36%, P < 0.001) in 2011–2012 compared to 2005–2009. However, the percentage of reports with trial design decreased from 4.45% to 3.25% (P = 0.011). Few reports described the blinding methods, and there was a decreasing tendency (4.77% vs 2.48%, P < 0.001). There was a similar decreasing tendency on the reporting of funding (6.53% vs 5.00%, P = 0.007). There were no significant differences in the other CONSORT items. In terms of Jadad Score, the proportion of reports with a score of 2 was markedly increased (15.15% vs 19.71%, P < 0.001).ConclusionsAlthough the quality of reporting RCTs of TCM was improved in 2011–2012 compared to 2005–2009, the percentages of high-quality reports are both very low in terms of Jadad score. There is a need for improving standards for reporting RCTs in China.

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