ABSTRACT
OBJECTIVE:To study the effects of ginsenoside CK combined with 5-fluorouracil (5-FU) on the proliferation, apoptosis and epithelial mesenchymal transition (EMT) of human pancreatic cancer PANC-1 cells. METHODS:PANC-1 cells of logarithmic growth phase were randomly divided into blank control group,ginsenoside CK group (30 mg/L),5-FU group (25 mg/L)and combination group(ginsenoside CK 30 mg/L+5-FU 25 mg/L). MTT method was used to detect the cell proliferation in-hibition rate in each group after 24,48,72 h;flow cytometry was used to detect the cell apoptosis rate after 48 h;enzyme-linked immunosorbent assay was used to detect the fibronectin expression in cells after 24,48,72,96 h;and Western blot was used to detect the expressions of vimentin,N-cadherin,E-cadherin,protein kinase(Akt)and phosphorylated Akt(p-Akt)protein in cells after 48 h. RESULTS:Compared with blank control group,the cell proliferation inhibition rate,early and late apoptotic rates,pro-tein expression level of E-cadherin in ginsenoside CK group,5-FU group and combination group were obviously increased (P<0.05),while the protein expression levels of fibronectin,vimentin,N-cadherin,and p-Akt/Akt levels were obviously decreased (P<0.05);the effects of above-mentioned indexes in combination group were superior to ginsenoside CK group and 5-FU group (P<0.05). CONCLUSIONS:Both ginsenoside CK and 5-FU can inhibit the proliferation of PANC-1 cells,induce their apoptosis and inhibit EMT,which may be associated with inhibiting phosphatidylinositol 3-kinase/Akt pathway. In addition,the combination of ginsenoside CK and 5-FU can produce a better effect.
ABSTRACT
The Aconiti Radix Cocta gel and Aconiti Radix Cocta combined with Paeoniae Radix Alba gel were administered to mice. Physiological saline was taken as perfusate. The perfusion rate was 2 μL•min⁻¹ and the microdialysis samples were collected every 0.5 h intervals for eight times. The six aconitine alkaloids concentration in perfusate were determined by HPLC-MS/MS. The concentration-time curves were plotted, and the pharmacokinetic parameters were calculated and analyzed by SPSS. The effects of Paeoniae Radix Alba on transdermal permeation role of six aconitine alkaloids in herb couple of Paeoniae Radix Alba-Aconiti Radix Cocta were investigated. According to the results, Tmax of the three mono-ester aconitum alkaloids of Aconiti Radix Cocta combined with Paeoniae Radix Alba groups were shortened, meanwhile, Cmax and AUC of benzoylaconine and benzoylhypaconine were increased. However, AUC of the three diester-type alkaloids were reduced, with Tmax of hypaconitine prolonged and Cmax lowered. The study suggested that the combined administration of Aconiti Radix Cocta and Paeoniae Radix Alba promoted the transdermal permeation of mono-ester aconitum alkaloids, and inhibited the absorption of parts of diester-type alkaloids. This study proved the decreasing toxicity and increasing efficacy of the combination of Aconiti Radix Cocta and Paeoniae Radix Alba on the transdermal permeation, and provided a reference for studies on the prescription combination regularity and relevant practices.
ABSTRACT
Objective: To study the anticoagulant effect of Shunaoxin Dropping Pill (SDP) alone or in combination with Warfarin sodium on platelet aggregation and provide the experimental support for the clinical safety of medication. Methods: Experiments were carried out in control group, low-dose SDP group, high-dose SDP group (45.36 and 90.72 mg/kg), and Warfarin sodium (clinical equivalent dose 0.4 mg/kg) group, Combined administration with low-dose SDP and high-dose SDP groups+clinical equivalent dose of Warfarin sodium. We determined the platelet aggregation rate of rats in the control group, low-dose SDP group, and high-dose SDP group in vitro by turbidimetry. We made iac administration of SDP and Warfarin sodium for 3 d, and took abdominal aortic blood for separating the platelets and used nephelometry for determining platelet aggregation rate; We separated serum and used semi-automatic coagulation analyzer to test APTT, PT, and TT. Results: Compared with the control group, SDP had the strong anti-platelet aggregation in vitro and could inhibit the increase of platelet aggregation in vivo slightly with the dose increasing. SDP could prolong APTT, PT, and PT; Compared with the single drug group, the combination therapy had no obvious effect on the platelet aggregation but could significantly extend the APTT, PT, and TT. Conclusion: SDP has some inhibition on platelet aggregation with anticoagulant effect; Combined with Warfarin sodium, SDP has a synergistic interaction on anticoagulant effect with Warfarin sodium.
ABSTRACT
Objective: To investigate the effects of curcumin combined with oxaliplatin on the human colon cancer cells LoVo xenografted tumor in nude mice and to explore the mechanism. Methods: Nude mice were implanted with human colon cancer LoVo cells. All tumor-bearing mice were randomly divided into four groups and treated with vehicle, 50 mg/kg curcumin, 25 mg/kg oxaliplatin, and their combination (50 mg/kg curcumin + 25 mg/kg oxaliplatin) by ip injection once every other day individually. After continuous administration of drug treatment for 11 times, the weights of nude mice were recorded, the stripping tumor weight was monitored, and the tumor volume and tumor inhibitory rates were calculated. The enucleation of eyeball for taking blood and blood routine examination were carried out and the function of liver and kidney was detected. Tumor cell cycle and apoptosis rate were assayed by flow cytometry. The pathological morphology of tumor was analyzed by HE staining. The apoptosis related gene expression was detected by RT-PCR. Results: Tumor inhibitory rates of curcumin, oxaliplatin, and curcumin + oxaliplatin groups were 59.47%, 55.49%, and 70.56%, respectively. Curcumin combination with oxaliplatin did not influence the blood system, liver, and kidneys in nude mice. Combination of curcumin and oxaliplatin could effectively inhibit the tumor growth (P < 0.05), interfere with cell cycle arresting at S and G2/M phases (P < 0.05, 0.01), and promote the expression of bax (P < 0.01) in tumor-bearing nude mice. Conclusion: Combination of curcumin and oxaliplatin could synergistically inhibit the growth of LoVo colonic xenografts in nude mice.
ABSTRACT
OBJECTIVES: For the relapse prevention in alcohol dependence, a lot of studies suggested that combined administration of two or more drugs which have different mechanism of action is more effective than each drug alone. In order to investigate the effectiveness of combined administration of naltrexone and acamprosate in comparison with naltrexone alone, this study was carried out by comparing the amount of alcohol intake in C57BL/6 mice co-administered with naltrexone and acamprosate with that in C57BL/6 mice with naltrexone alone. METHODS: In 42 C57BL/6 mice in the state of alcohol dependence, naltrexone 0.025mg/kg or 1.0mg/kg alone or with acamprosate 50mg/kg or 200mg/kg were administrated for ten days. The amounts of alcohol consumption for 2 hour, water consumption for 22 hours, and food intake for 24 hours were measured. RESULTS: 1) A significant reduction of alcohol intake for 2 hours was observed when the mice were treated with naltrexone 0.025mg/kg or 1.0mg/kg and acamprosate 50mg/kg or 200mg/kg simultaneously compared with naltrexone 0.025mg/kg or 1.0mg/kg alone. This effect was significant on the eighth and tenth days of drug administration. 2) Naltrexone administration of 1.0mg/kg was significantly more effective than that of 0.025 mg/kg in reducing alcohol intake from the second day of drug administration up to the tenth day. 3) No significant difference was revealed between the effect of naltrexone alone and that of naltrexone with acamprosate on 22 hour water consumption and 24 hour food intake. CONCLUSION: From these results, it is suggested that the effect of combined treatment with naltrexone and acamprosate is superior to that of naltrexone alone in prevention of relapse in alcohol dependence.