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Objective::To observe the synergistic effect and mechanism of Yiqi Jianpi Huayu (YQJPHY) recipe combined with 5-fluorouracil (5-FU) on inhibiting gastric cancer growth, and investigate its possible mechanism through polarization direction of tumor-associated macrophages (TAMs) in tumor micro-environment. Method::A total of forty 615 mice were randomly divided into four groups including control group, YQJPHY(25 g·kg-1) group, 5-FU (25 mg·kg-1) group and combined group (YQJPHY plus 5-FU), with 10 mice in each group. The gastric cancer transplantation model was induced by axillary inoculation of MFC gastric cancer cells. Changes in tumor pathology were observed with hematoxylin-eosin staining (HE) method. The contents of M1 and M2 TAMs in tumor tissues were determined with flow cytometry, while the expression of CD206 in tumor was observed with immunohistochemistry. The mRNA expressions of TAM-related genes including interleukin-1β(IL-1β), interleukin-12(IL-12), tumor necrosis factor-α(TNF-α), arginase-1(Arg1), and chitinase 3-like 3(Ym1) were detected by using quantitative real-time polymerase chain reaction (Real-time PCR). Furthermore, the mRNA and protein expressions of epithelial-mesenchymal transition (EMT) related epithelial calcium adhesion protein(E-cadherin), nervous calcium adhesion protein(N-cadherin), Zinc finger transcription factor Slug, Snail and Waveform protein (Vimentin) were detected with Real-time PCR and Western blot, respectively. Result::The gastric cancer cells in tumors were distributed in nest and/or flaky shape, with fibroblastic connective tissue reaction and inflammatory cells infiltrated in interstitium. Coagulative necrosis of tumor was observed in various treatment groups. The amount of residual cancer cells in mouse was as follows from largest to smallest: control group>YQJPHY group>5-FU group>combined group. Immunohistochemical studies showed that all treatment groups can reduce the expression of CD206 in the tumor, and the effect was most obvious in the combined group. The contents of M2-TAM in all treatment groups were lower than those in control group(P<0.05, P<0.01), and the most significant difference in the content of M2-TAMs was shown between the control group and the combined group. The contents of M1 TAMs were increased in YQJPHY and combined groups(P<0.05, P<0.01), with the largest incremental range in YQJPHY group. The expressions of Arg1 and Ym1 in YQJPHY and combined groups were lower, while IL-1β, TNF-α and IL-12 levels were higher than those in control group(P<0.05). The mRNA expressions of IL-1β, IL-12 and TNF-α in the combined group were significantly higher, while Arg1 and Ym1 mRNA expression levels were lower than those in the 5-FU group(P<0.05). As compared with the control group, the mRNA and protein expression levels of E-cadherin were up-regulated(P<0.05), while the mRNA expression levels of N-cadherin and Vimentin were down-regulation in the YQJPHY group (P<0.05), E-cadherin mRNA and protein expression levels were up-regulated, while N-cadherin, Slug, Snail, Vimentin mRNA expression as well as N-cadherin and Slug protein expression levels were down-regulated in the combined group(P<0.05). As compared with the 5-FU group, the mRNA and protein expression levels of E-cadherin were up-regulated(P<0.05), while the mRNA and protein expression levels of N-cadherin, Slug and Vimentin were down-regulated in the combined group(P<0.05). Conclusion::YQJPHY has an inhibitory effect on the growth of gastric cancer, and after being combined with 5-FU, it has a good synergistic effect on inhibiting the growth of gastric cancer and decreasing EMT. The mechanism may be related to promoting the conversion from M2-TAMs to M1-TAMs in gastric tumor micro-environment.
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Objective To explore the effects of Yiqi Jianpi decoction on inflammatory reaction, immune function and nutritional status in patients after surgery of laparoscopic rectal cancer. Methods Eighty-two patients with post-operative laparoscopic rectal cancer resection admitted to Pingxiang People's Hospital from June 2017 to March 2019 were enrolled, and according to whether traditional Chinese medicine (TCM) was used or not, they were divided into a western medicine treatment control group (control group) and a combined traditional Chinese and western medicine treatment group (combined group), 41 cases in each group. The control group was treated with symptomatic conventional western therapy, while the combined group was additionally treated with Yiqi Jianpi decoction based on the conventional western treatment as in the control group; the composition of the decoction: hedyotis herba, herba agrimoniae, radix astragali each 30 g; radix codonopsis, ganoderma lucidum each 20 g; rizoma atractylodes, poria cocos and prunella chinensis 15 g each; pinellia ternata 9 g, licorice root 6 g; all the above ingredients were together boiled with water and the fluid (decoction) was filtered, 150 mL once orally taken, twice a day, 21 days constituting one therapeutic course, and the clinical efficacy was evaluated after 1 course of therapy. The changes of TCM syndrome score, simple health situation scale (SF-36) score, inflammatory indexes, immune function and nutritional status of the two groups were observed before and after treatment. Results After treatment, the levels of TCM syndrome score, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and CD8+ in the two groups were significantly lower than those before treatment, while the levels of SF-36 score, CD4+, CD4+/CD8+, transferrin (TRF) and albumin (Alb) were significantly higher than those before treatment (all P < 0.05), and the degree of changes in the combined group were more significant than those in control group [TCM syndrome score: 3.79±2.22 vs. 6.86±2.02, SF-36 score:75.18±4.13 vs. 64.17±4.01, CRP (mg/L): 4.54±1.31 vs. 5.71±2.21, IL-6 (μg/L): 20.21±2.21 vs. 26.12±2.13, TNF-α (μg/L): 33.04±4.56 vs. 36.41±3.23, CD4+: 0.37±0.03 vs. 0.35±0.03, CD8+: 0.25±0.03 vs. 0.28±0.03, CD4+/CD8+: 1.51±0.39 vs. 1.19±0.37, TRF (g/L): 3.05±0.41 vs. 2.28±0.42, Alb (g/L): 43.88±2.28 vs. 39.86±2.03, all P < 0.05]. Conclusion Yiqi Jianpi decoction in the treatment of patients after surgery of laparoscopic rectal cancer can effectively promote the recovery of gastrointestinal function, reduce the inflammatory reaction, elevate the immune function and improve clinical prognosis.
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Objective:To discuss the effect of Yiqi Jianpi Huayu recipe (YQJPHY) combined with 5-fluorouracil(5-FU) on the growth and immune function of subcutaneous transplanted tumor in MFC tumor bearing 615 mice. Method:Twenty-four mice were inoculated subcutaneously to establish the transplanted tumor model of gastric cancer in mice, and then randomly divided into model control group, YQJPHY (20 g·kg-1)group, 5-FU (25 mg·kg-1) group and (YQJPHY+5-FU) combined group, with 6 rats in each group. After the last administration, the transplanted tumor, spleen and thymus were stripped completely. The tumor inhibition rate, thymus and spleen index were calculated. Flow cytometry was used to determine the content of myeloid-derived suppressor cells (MDSCs) and its subtype polykaryotype cells (PMN-MDSC), single karyotype cells (M-MDSC) in both peripheral blood and tumor tissue, and macrophages and their M1 type, M2 type, T lymphocyte, B lymphocyte, and natural killer cells (NK cells) in peripheral blood. Expressions of arginase-1(Arg-1) and inducible nitric oxide synthesis (iNOS) gene in tumor tissues were detected by Real-time PCR. Result:Compared with model control group, the weight of mice in YQJPHY group increased, whereas the weight of tumor, the weight of tumor, the index of thymus and spleen decreased in 5-FU group(PPPPPPPP+,CD4+,CD8+ T cell group decreased(PPPPPPConclusion:YQJPHY can better inhibit the growth of subcutaneous transplanted tumor when combined with 5-FU, and improve immune status after chemotherapy. The mechanism may be related to the decrease of MDSCs content and the increase of T cell and macrophages content.
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Objective To explore the effect of Yiqi-jianpi-jiedu recipe decoction containing serum on Oxaliplatin-induced HepG2 Human hepatoma cell survivin, caspase-3, caspase-9 expression. Methods The serum pharmacological method was used to prepare nourishing Qi and invigorating spleen decoction containing serum of rat. The HepG2 human hepatoma cells were divided into Chinese herb containing serum group, chemotherapy with Oxaliplatin (OXA) group and the combination group (medicine containing serum and OXA), and the blank group without drugs. Apply MTT assay, Western Blotting method and RT-PCR method to detect the cell inhibition rate and survivin, caspase-3, caspase-9 protein and gene expression changes. Results Compared with the blank group, the inhibition rate of HepG2 Human hepatoma cell was significantly higher in Chinese herb containing serum group, chemotherapy group and the combination group (P < 0.05). Compared with thechemotherapy group and Chinese herb containing serum group, the Survivin (0.151 ± 0.054 vs. 0.288 ± 0.089, 0.375 ± 0.063) and the expression of Survivin mRNA (0.205 ± 0.091 vs. 0.487 ± 0.073, 0.725 ± 0.092) of the conbination group downgraded significantly lower (P < 0.05 or P< 0.01). Compared with chemotherapy group and Chinese herb containing serum group, the caspase-3 (0.821 ± 0.079 vs. 0.634 ± 0.098, 0.487 ± 0.102), caspase-9 (0.901 ± 0.047 vs. 0.709 ± 0.054, 0.402 ± 0.012) expression, caspase-3 mRNA (1.928 ± 0.226 vs. 1.564 ± 0.195, 1.287 ± 0.312) and caspase-9 mRNA (2.063 ± 0.517 vs. 1.536 ± 0.084, 1.019 ± 0.182) expression of the conbination group upgraded significantly higher (P < 0.05 or P < 0.01). Conclusions Nourishing-Qi and invigorating spleen decoction containing serum may affect Oxaliplatin-induced HepG2 apoptosis mechanism through increasing the suppression on Survivin and promoting the expression of caspase-3 and caspase-9 protein and genes. This research provided important experimental basis for clinical application of traditional Chinese medicine treating liver cancer.
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Objective:To investigate the inhibitory effect and the related mechanism of Yiqi Jianpi Fang on aberrant crypt focus (ACF) in Wister rat colorectal cancer model.Methods:50 Wistar rats were randomly divided into 5 groups:TCM low dose group(TCM solution diluted 3 times,5 mL/kg daily gastric volume),TCM middle dose group (5 mL/kg daily gastric volume),TCM high dose group (15 mL/kg daily gastric volume),model group,normal group.With 10 rats in each group.The colorectal tissues were observed under microscope after methylene blue staining by immunohistochemistry method.Results:Compared with the model group,the number of ACF and large ACF in each TCM group were decreased (P＜0.05),and the number of ACF in the TCM middle dose group reduced most obvious,and the difference was statistically significant (P＜0.05).The proliferation indexs of PCNA in intestinal gland cells 24 h and 48 h after modeling in the TCM groups were higher than those in the model group,and the difference was statistically significant(P＜0.05).The apoptosis index of intestinal gland cells 24 h and 48 h after modeling in the TCM groups were higher than those in the model group,and the difference was statistically significant(P＜0.05).The ectopic expression of β-catenin in TCM groups were lower than that in the model group,and it was highest in the high dose group,than was the low dose group,and the middle group was lowest(P＜0.05).The expression of MMP-7 in TCM groups were lower than that in the model group,and it was highest in the low dose group,than was the high dose group,and the middle dose group was lowest (P＜0.05).Conclusion:Yiqi Jianpi Fang can significantly reduce the number of ACF in Wister rats,inhibit the activation of Wnt signaling in colorectal cancer,reduce the incidence of colorectal cancer,and have a certain preventive effect.
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OBJECTIVE@#To observe the effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.@*METHODS@#Human intestinal cancer cell HT29 xenograft of nude mice model was established. The expression of EGF, VEGF, gastric cancer tumor growth in mice were observed.@*RESULTS@#Protein kinase C expression in in the Yiqi Jianpi group and Yiqi Jianpi anti-tumor group was significantly better than the model group (P<0.01, P<0.05). There was significantly more apoptotic cells in Yiqi Jianpi anti-tumor group than Yiqi Jianpi group and model group (P<0.01). Epidermal growth factor and vascular endothelial growth factor expression in Yiqi Jianpi group was significantly lower than Yiqi Jianpi group and model group (P<0.05).@*CONCLUSIONS@#Tumor can inhibit the expression of PKC inhibition. Yiqi Jianpi and anticancer treatment can reduce this inhibition. Besides this treatment can also inhibit expression of tumor related genes such as epidermal growth factor and vascular endothelial growth factor.