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Based on UPLC-Q-orbitrap-MS and biological network analysis tools, the mechanism of Xihuang Pill in improving hyperplasia of mammary glands was systematically analyzed. The rat model of hyperplasia of mammary glands was established by intramuscular injection of estradiol benzoate and progesterone. LC-MS tissue metabolomics was used to explore the key metabolites and metabolic pathways of Xihuang Pill in improving hyperplasia of mammary glands in rat. The network analysis of the key metabolites regulated by Xihuang Pill was carried out by integrating biological network analysis tools, focusing on the key metabolic pathways, and exploring the potential targets of Xihuang Pill to improve hyperplasia of mammary glands. Compared with the control group, there were significant differences in the content of 49 differential metabolites in the tissues of the model group (P < 0.05). Xihuang Pills could significantly call back 17 metabolites such as L-alanine, threonine, indole-3-carboxylic aldehyde, lysine, arginine, alanylleucine, glycyltyrosine, γ-glutamyl leucine, vitamin B3, serine leucine, threonine leucine, isoleucine glutamic acid, γ-glutamyl tyrosine, decanoyl-L-carnitine, uric acid, leucylleucine, S-adenosyl-methionine. Further network analysis and literature research on the key metabolites regulated by Xihuang Pills showed that the AGE-RAGE signaling pathway may be one of the important pathways for Xihuang Pills to improve hyperplasia of mammary glands. STAT3, MAPK1, EGFR, CASP3, CASP8, PRKCA and JUN in the AGE-RAGE signaling pathway may be potential targets for Xihuang Pills to improve hyperplasia of mammary glands. The animal experiment operations involved in this paper follow the provisions of the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine and pass the ethical review of animal experiments (approval number: 2022-705).
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Our studies were aimed to explore the effect and mechanism of the inhibition of the formation of vasculogenic mimicry (VM) in human glioblastoma cells by Xihuang pill (XHP) medicated serum through regulating the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. The medicated serum of XHP was prepared by gavage for 7 days to male SD rats (approval number of animal experiment ethics: 202105A051). The hypoxia model of U251 cells was established using 200 μmol·L-1 of CoCl2. After treatment with XHP-medicated serum, cell viability and proliferation of U251 cells were detected by CCK-8 and cell cloning experiment. Cell apoptosis and cell cycle of U251 cells were determined by flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell invasion assay. The formation of VM was assessed by three-dimensional cell culture of U251 cells. The protein expression levels of HIF-1α, VEGFA, VEGFR2, phosphorylated-VEGFR2 (p-VEGFR2), vascular endothelial-cadherin (VE-cadherin), Eph receptor tyrosine kinases A2 (EphA2), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 14 (MMP14) and laminin γ2 in U251 cells were detected by Western blot. The results showed that 10% XHP-medicated serum had little effect on the cell viability, proliferation, apoptosis and cell cycle of U251 cells under hypoxia. Compared with the model group, 10% XHP-medicated serum at 1.0, 1.5 and 2.0 h significantly decreased the migration rate (P < 0.01) and the number of invading U251 cells (P < 0.01). 10% XHP-medicated serum at 2.0 h significantly suppressed the formation of VM tubular structures in U251 cells under the condition of hypoxia (P < 0.01). Western blot experiment showed that 10% XHP-medicated serum significantly down-regulated the expression of HIF-1α, VEGFA, phospho-VEGFR2, VE-cadherin, EphA2 and MMP14 proteins (P < 0.05). In conclusion, XHP could inhibit the formation of VM in human glioblastoma U251 cells to suppress the angiogenesis by down-regulating the HIF-1α/VEGFA/VEGFR2 signaling pathway.
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Objective To study the differentially expressed microRNAs ( miRNAs) in breast canc-er formalin-fixed, paraffin-embedded ( FFPE) tissue and the effect of Xihuang Pill extract on the expression of candidate miRNAs in breast cancer cell line in vitro. Methods Microarray was used to detect the differ-entially expressed miRNAs in breast cancer tissues, adjacent tissues and cancer tissues with different molec-ular types, and the results of unsupervised cluster analysis were processed by cluster software. Real-time fluorescence quantitative polymerase chain reaction ( qPCR) was used to detect the expression of candidate miRNAs in 106 breast cancer tissues, 22 paracancerous tissues and 66 benigh breast lesions. The extract of Xihuang Pill interfered with T-47D cells and MDA-MB-231 cells, then the expression of candidate miRNAs in those cells were detected by qPCR. Results The microarray results showed that the expression of miR-130b was higher in cancer tissues than in adjacent tissues (P<0. 05). The expression of miR-205 in basal-like cancer tissues with higher malignancy was significantly lower than that in luminal cancer tissues ( P<0. 05). qPCR showed that the expression miR-130b in cancer tissues (t=6. 123, P=0. 000) and adjacent tissues (t= -3. 375, P=0. 001) were significantly higher than that in benigh lesion tissues, and the ex-pression of miR-205 in cancer tissues was significantly lower than that in benigh lesion tissues ( t =-2. 073, P=0. 041). Cell experiment in vitro showed that the expression of miR-130b in T-47D cells de-creased after the intervention of Xihuang Pill extract (t=4. 341, P=0. 012) , while the expression of miR-205 in MDA-MB-231 cells increased after the intervention of Xihuang Pill extract ( t = -3. 266, P =0. 031). Conclusions The increase of miR-130b and the decrease of miR-205 are related to the occur-rence and development of breast cancer. The increase of miR-130b and the decrease of miR-205 may be the one of anti-tumor ways of Xihuang Pill.
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To study the effect of serum containing Xihuang pill on the proliferation of human breast cancer cell lines MDA-MB-435 and MCF-7 and the gene and protein expressions of Bcl-2, Bax, TP53, in order to explore the effect and mechanism of Xihuang pill in resisting breast cancer. The serum of the rats was prepared by the method of MTT assay. The expressions of Bcl-2 and Bax were detected by RT-PCR. The serum levels of Bcl-2 and Bax and the mRNA expression of TP53 were detected by immunofluorescence. The rats with serum containing Xihuang pill could inhibit the proliferation of MDA-MB-435 cells and MCF-7 cells (<0.05). The serum containing Xihuang pill increased TP53 and Bax in MDA-MB-435 cells (<0.05), and the ratio of Bcl-2/Bax was decreased (<0.05). Meanwhile, the serum containing Xihuang pill could up-regulate the mRNA expression of Bax in MCF-7 cells and decrease the expression of Bcl (<0.05), but there was no significant difference between the expression of TP53mRNA and Bax protein expressions after the treatment of MCF-7 cells with Xihuang pill serum. Serum containing Xihuang pill can induce the apoptosis of human breast cancer cells, and the mechanism of estrogen receptor-negative breast cancer cell apoptosis may be induced by up-regulating the mRNA expression of TP53, which can induce the expression of Bax and promote the metastasis of Bax to mitochondria, and ultimately play the role of inducing apoptosis.
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Objective To investigate the effect of Xihuang Pill on the curative effect of paclitaxel combined with platinum based neoadjuvant chemotherapy in patients with advanced cervical cancer after operation.Methods 80 cases of patients with advanced cervical cancer treated in our hospitalfrom January 2014 to January 2017 were enrolled in the study.By random number table method,the patients were divided into the observation group and the control group with 40 cases in each group,and all patients were treated with radical hysterectomy.After operation,the control group were treated with paclitaxel and platinum (cisplatin) based neoadjuvant chemotherapy,while the observation group were treated with Xihuang Pill and platinum based neoadjuvant chemotherapy.The effective rate of chemotherapy,survival rate and recurrence rate were compared between the two groups.The levels ofT lymphocyte subsets (CD3+,CD4+,CD8+) and immunoglobulin (IgA,IgG,IgM) in two groups were determined before and after chemotherapy.The quality of life and cancer pain degree were evaluated with the Kamofsky Performance Scale (KPS) and the numeric rating scale (NRS),and adverse reactions were recorded.Results The effective rate of chemotherapy was slightly higher in the observation group than the control group (87.50％ vs 77.50％).Three months and six months after chemotherapy,the survival rate and recurrence rate showed no significant difference between the two groups.After chemotherapy,percentages of CD3+ and CD4+,levels of IgA,IgG and IgM were significantly higher in the observation group than the control group (P ＜ 0.05),and the percentage of CD8+ was lower than the control group (P ＜ 0.05).After treatment,KPS score of the observation group was significantly higher than the control group,and NRS score was significantly lower than the control group (P ＜ 0.05).The incidence of adverse reactions was significantly lower in the observation group than the control group (7.50％ vs 25.00％) (P ＜ 0.05).Conclusion Xihuang Pill combined with cisplatin based neoadjuvant chemotherapy is effective in the treatment of advanced cervical cancer after operation.The regimen can improve the immune function and quality of life,relieve pain degree and reduce adverse reactions.It will not increase the short-term survival rate and recurrence rate,and long-term efficacy needs further study.
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Objective To investigate the effect of Xihuang Pill on the curative effect of paclitaxel combined with platinum based neoadjuvant chemotherapy in patients with advanced cervical cancer after operation.Methods 80 cases of patients with advanced cervical cancer treated in our hospitalfrom January 2014 to January 2017 were enrolled in the study.By random number table method,the patients were divided into the observation group and the control group with 40 cases in each group,and all patients were treated with radical hysterectomy.After operation,the control group were treated with paclitaxel and platinum (cisplatin) based neoadjuvant chemotherapy,while the observation group were treated with Xihuang Pill and platinum based neoadjuvant chemotherapy.The effective rate of chemotherapy,survival rate and recurrence rate were compared between the two groups.The levels ofT lymphocyte subsets (CD3+,CD4+,CD8+) and immunoglobulin (IgA,IgG,IgM) in two groups were determined before and after chemotherapy.The quality of life and cancer pain degree were evaluated with the Kamofsky Performance Scale (KPS) and the numeric rating scale (NRS),and adverse reactions were recorded.Results The effective rate of chemotherapy was slightly higher in the observation group than the control group (87.50％ vs 77.50％).Three months and six months after chemotherapy,the survival rate and recurrence rate showed no significant difference between the two groups.After chemotherapy,percentages of CD3+ and CD4+,levels of IgA,IgG and IgM were significantly higher in the observation group than the control group (P ＜ 0.05),and the percentage of CD8+ was lower than the control group (P ＜ 0.05).After treatment,KPS score of the observation group was significantly higher than the control group,and NRS score was significantly lower than the control group (P ＜ 0.05).The incidence of adverse reactions was significantly lower in the observation group than the control group (7.50％ vs 25.00％) (P ＜ 0.05).Conclusion Xihuang Pill combined with cisplatin based neoadjuvant chemotherapy is effective in the treatment of advanced cervical cancer after operation.The regimen can improve the immune function and quality of life,relieve pain degree and reduce adverse reactions.It will not increase the short-term survival rate and recurrence rate,and long-term efficacy needs further study.
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Xihuang pill,a famous anticancer traditional Chinese medicine formula,has curative effect in clinical application. It can inhibit the growth and invasion of tumor cells and cancer stem cells,prevent angiogenesis,and reverse the tumor immunosup-pressive microenvironment. This review summarizes the reported Xihuang pill' s anticancer mechanism and clinical application on colorectal cancer,breast cancer,liver cancer,so as to provide a reference for the further research and development on anticancer ap-plication of Xihuang pill.
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This study was aimed to explore the antitumor effect of volatile oil of X ihuang pill and its immune mecha-nism in order to screen the antitumor active site of Xihuang pill. Among 70 female Wistar rats, 10 rats were random-ly selected as the blank control group; and the other 60 rats was used in the establishment of walker 256 breast can-cer cell tumor-bearing rat models. The model rats were randomly divided into the negative control group (model group), high-dose volatile oil group, middle-dose volatile oil group, low-dose volatile oil group, high-dose Xihuang pill group, and lentinan group (positive control group), with 10 rats in each group. The intragastric administration was given twice a day for 14 days. Blood was taken from the abdominal aorta. Tumor tissues was removed and weighed to calculate the tumor inhibitory rate. ELISA method was used to detect the level of IL-2, IL-6, IL-10, IFN-γ and TGF-β in peripheral blood. The flow cytometry was used to detect the content of CD3+ T cell, CD4+ T cell, CD8+ T cell, and B7-1 cell (CD80). The results showed that the tumor inhibitory rates of volatile oil of high-dose group and middle-dose group were 28.4% and 24.1%, respectively. Compared with the model group, the average level of IL-2 and IFN-γ of volatile oil of high-dose group and middle-dose group and CD3+ T cell, CD8+ T cell, B7-1 cell con-tent were obviously increased (P< 0.05). It was concluded that volatile oil of Xihuang pill had certain antitumor ef-fect, which was one of the antitumor active sites of Xihuang pill. The volatile oil of Xihuang pill upregulates the lev-els of IL-2 and IFN-γ, as well as the contents of CD3+ T cell, CD8+ T cell, B7-1 cell in order to increase the im-mune clearance function of tumor-bearing rats.
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AIM:To evaluate treatment value of Xihuang Pill combined gemeitabine for advanced pancreatic cancer patients.METHODS:Thirty-two patients with advanced pancreatic cancer were randomly divided into A group and B group,treated with gemcitabine chemotherapy and traditional Chinese medicine Xihuang Pill+chemotherapy treatment,respectively.The changes of the solid tumor,serum CA19-9,physical status,clinical symptoms and toxicity were observed.RESULTS:B group(Xihuang Pill combined with gemcitabine)clinical return ratio (CR+PR+NC)was better than A group(gemcitabine).There was significant difference between two groups in the reduction of serum CA19-9 level,Karuofsky score increased,the rate of symptom improvement,Leukopenia reduction(P＜0.05).CONCLUSION:Integrating Xihuang Pill and gemcitabine in the treatment of advanced pancreatic cancer:delaying of tumor growth,reducing of CA19-9 level,improving of the clinical symptoms and life quality of patients,reducing of neutropenia in patients(chemotherapy-induced toxicity),shows good clinical benefit response.
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Objective: To observe the clinical effects on advanced esophageal cancer by combined Xihuang Pill with chemotherapy. Methods: Dividing 35 advanced esophageal cancer cases randomly into two groups: 18 cases in the treatment group and 17 cases in the control group. Cases in the control group were treated by nedaplatin 40mg/m2,d1,2; 5-Fu400mg/m2,d1-5; CF200 mg/m2,d1-5. While the treatment with Xihuang Pill combined. The difference of quality of life, hematological toxicity, efficacy and symptoms between the two groups was observed. Results: The quality of life, remission rate of some symptom in the treatment group were much better than the control group, and the hematological toxicity and efficacy were the same. Conclusion: Xihuang Pill could improve the quality of life of advanced esophageal cancer patient, and alleviate some symptoms.
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Objective:To observe the clinical effect of Xihuang Pill in treatingadvanced primary liver caner. Methods: 23 cases of advanced primary liver caner were enrolled in the research. Two courses of Xihuang Pill were given orally (21d per course). The patients' quality of life (QOL) and clinical manifestations were recorded before and after the treatment. Results: QOL was improved in patients after the treatment. Clinical symptoms, such as abdominal distention, poor appetite and cancer pain, were also relieved. The above changes were statistically significant (P
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AIM:To evaluate treatment value of Xihuang Pill combined gemcitabine for advanced pancreatic cancer patients.METHODS:Thirty-two patients with advanced pancreatic cancer were randomly divided into A group and B group,treated with gemcitabine chemotherapy and traditional Chinese medicine Xihuang Pill+chemotherapy treatment,respectively.The changes of the solid tumor,serum CA19-9,physical status,clinical symptoms and toxicity were observed.RESULTS:B group(Xihuang Pill combined with gemcitabine)clinical return ratio(CR+PR+NC)was better than A group(gemcitabine).There was significant difference between two groups in the reduction of serum CA19-9 level,Karnofsky score increased,the rate of symptom improvement,Leukopenia reduction(P