BackgroundMultidrug resistance (MDR) frequently contributes to the failure of chemotherapeutic treatments in patients diagnosed with hepatocellular carcinoma (HCC). Revealing the molecular mechanism of MDR is indispensable for the development of effective chemotherapeutic drugs.PurposeDue to the low-toxicity modulators to inhibit MDR, we considered that Kanglaite (KLT) is a potential agent for reversing MDR in HCC.Materials and MethodsBEL-7402/5-fluorouracil (5-FU) and HepG2/adriamycin (ADM) were analyzed for cell viability, colony formation assay, cell scratch assay, and cell cycle analysis and apoptosis assay by flow cytometry. The expression of PARP, caspase-3, Bax, Bcl-2, CDC25C, Cyclin B1 and phosphorylation of PTEN, PI3K, and AKT in HepG2/ADM cells were detected by western blotting.ResultsThe proliferation of drug-resistant cell lines BEL-7402/5-FU and HepG2/ADM pretreated with KLT was significantly inhibited when compared with drug alone. KLT could increase the accumulation of ADM in HepG2/ADM cells. In this study, we found that KLT treatment notably reduced cell viability, induced apoptosis and cell cycle arrest in human HepG2/ADM and BEL-7402/5-FU cells, and effectively reversed the MDR by p-glycoprotein (P-gp) inhibition. Moreover, KLT decreased the phosphorylation of AKT and PI3K in KLT-treated HepG2/ADM cells. These data together implied that KLT might reverse drug resistance in HCC by blocking the PI3K/AKT signaling.ConclusionWe demonstrated that KLT reversed MDR of human HCC by inducing apoptosis and cell cycle arrest via the PI3K/AKT signaling pathway.
Background:The aim of this study was to evaluate effects of Shen-Cao granules for the prevention of thrombocytopenia caused by anticancer chemotherapy.Methods:In this prospective study, a total of 200 patients with various malignant tumors were enrolled and evenly divided into a Shen-Cao granule treatment (n = 100) and a control group (n = 100). After 2 cycles chemotherapy with any combination of platinum-based drugs (cisplatin, carboplatin, and nedaplatin), the blood platelet (PLT) counts, levels of the PLT production regulator thrombopoietin (TPO), PLT aggregation rates, and the PLT activation marker CD62P expressions were monitored for 2 weeks.Results:During 2 weeks of post-chemotherapy, the mean values of the minimum PLT count were 49.65 ± 7.35 × 109/L in the treatment group and 31.56 ± 9.32 × 109/L in the control group. The PLT count in the treatment group reached the lowest value 1.8 days later and recovered to a concentration ≥100 × 109/L 3 days earlier than in the control group. The concentrations of the TPO were 71.43 ± 1.74 and 87.24 ± 0.92 ng/mL in the treatment group and 65.75 ± 1.39 and 67.75 ± 0.67 ng/mL in the control group at 7 and 14 days post-chemotherapy, respectively. The maximum PLT aggregation rate declined after chemotherapy in the treatment group from 58.14 ± 11.46% to 52.89 ± 10.52%, while it increased in the control group from 56.94 ± 10.55% to 61.75 ± 12.26%. Coordinately, the expression of CD62P in the treatment group decreased from 6.17 ± 0.59% to 4.89 ± 0.72%, while it increased from 6.09 ± 0.75% to 7.75 ± 0.67% in the control group.Conclusion:Our study demonstrated that Shen-Cao granule treatment alleviated thrombocytopenia after chemotherapy, and reduced tumor-induced PLT activation and aggregation.
Purpose: To investigate the effect of Yugan Sanjie decoction on the expressions of regulatory T cells (Tregs), serum P21 protein and vascular endothelial growth factor (VEGF) in mice with hepatocellular carcinoma. Methods: A total of forty specific-pathogen-free (SPF) Kunming mice were randomly assigned to four groups of 10 mice each. Except for normal control group, the other three groups were transfected with hepatoma-22 (H22) cells to establish a mouse model of liver cancer. Mice in the cyclophosphamide group was given cyclophosphamide at a dose of 20 mg/kg daily intragastrically, while those in decoction group were treated with Yugan Sanjie decoction (0.4 ml/kg/day) intraperitoneally. After 30 days of treatment, serum levels of CD4+ Th17, CD4+CD25+ Treg, Th17/Treg, TNF-α, and VEGF were determined. Results: There was lower serum level of CD4+ Th17 in the decoction group than in negative control and cyclophosphamide groups (p < 0.05). However, higher serum levels of CD4+CD25+ Treg and Th17/Treg were seen in the decoction group, relative to the negative control and cyclophosphamide groups (p < 0.05). Serum TNF-α was also markedly elevated in decoction group, when compared with negative control and cyclophosphamide groups (p < 0.05). Serum VEGF was markedly lower in decoction group than in negative control and cyclophosphamide groups, and was appreciably lower in cyclophosphamide group than in negative control group (p < 0.05). Conclusion: Yugan Sanjie decoction effectively alleviates clinical symptoms of LC, and improves immune function of mice by regulating serum levels of T lymphocytes. These findings provide scientific support for a new treatment strategy.
Background: To observe clinical effects of Shen Cao granules on thrombocytopenia in patients with gastrointestinal cancer undergoing chemotherapy. Patients and Methods: Patients under a FOLFIRI chemotherapy regimen (n = 92) were randomly divided into study and control groups (n = 46 for each group) and were given 10 g of Shen Cao granules and a placebo, respectively, once daily on chemotherapy treatment days. Platelet counts were measured every other day and any adverse reaction recorded during the study and at follow-up. Results: The incidence of thrombocytopenia (grades II-IV) in the study group was significantly decreased, and the length of hospitalization significantly reduced compared with the control group (11.21 ± 2.46 vs 15.34 ± 3.68 days, P < .05). The minimum numbers of post-chemotherapy platelets and the values of platelet counts 21 days after chemotherapy were significantly increased ([100.65 ± 63.16] × 109/L vs [60.21 ±37.22] × 109/L, P < .05; [267.81 ± 81.32] × 109/L vs [146.42 ± 70.54] × 109/L, P < .001), and the duration of thrombocytopenia and treatment with recombinant human interleukin-11 was significantly decreased in the Shen Cao treatment compared with the control group. No serious adverse events were observed. Conclusions: Shen Cao granules were effective in decreasing chemotherapy-induced thrombocytopenia, shortened the duration of thrombocytopenia, and reduced the length of hospital stay and costs.
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