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OBJECTIVES@#Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo.@*METHODS@#Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene.@*RESULTS@#The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT.@*CONCLUSION@#ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.
Subject(s)
Animals , Mice , Cell Line, Tumor , Cell Movement , Cell Proliferation , China , Gene Expression Regulation, Neoplastic , Mice, Nude , Neoplasm Invasiveness , Stomach Neoplasms/geneticsABSTRACT
Objective To discuss the application of endoscopic injection of lauromacrogol and methylene blue in sclerotherapy of esophageal varices. Methods The clinical data of 62 patients with esophageal varices underwent endoscopic treatment from June 2014 to February 2016 were collected, including 26 cases treated by endoscopic injection of lauromacrogol (A group) and 36 cases treated by endoscopic injection of lauromacrogol and methylene blue (B group). The treatment effects, success rate of hemostasis, safety, complications and follow-up recurrence were compared between the two groups. Results The total effective rate and success rate of emergency hemostasis in B group were slightly higher than those in A group (P > 0.05). The times of treatment for eliminating esophageal varices in B group was less than that in A group, and the duration of treatment was shorter than that in A group (P < 0.05). The long-term rebleeding rate and total bleeding rate in B group were lower than those in A group (P < 0.05). The incidence of postoperative complications and recurrence rate in B group were lower than those in A group (P < 0.05). Conclusion Endoscopic injection of lauromacrogol and methylene blue is effective in the treatment of esophageal varices, and the hemostatic effect is good. The incidence of postoperative complications and the recurrence rate are low.
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Objective To investigate clinical efficacy of Xiaotan Tongluo Gel combined with mecobalamin tablets in treating chemotherapy-induced peripheral neuropathy (CIPN). Methods Totally 67 cases of CIPN were divided into the treatment group (36 cases) and the control group (31 cases). Both groups were given mecobalamin tablets, 0.5 mg each time, three times a day, orally. Patients in the treatment group were treated with Xiaotan Tongluo Gel for external use at the same time. The patients in control group were treated with placebo gel for external use, 1 mL/cm2, rubbed on the skin 1 cm more than sensory obstruction in diameter. The treatment for both groups lasted for 14 d as a treatment course, and the treatment lasted for 2 courses. The changes of peripheral nerve toxicity, TCM syndrome scores and the nerve conduction velocity were observed in the two groups. Results On the 14th and 28th days of treatment, the total effective rates of peripheral nerve toxicity were 75.00% and 91.67% in the treatment group, and 38.71% and 67.74% in the control group, and the treatment group was significantly better than those of the control group (P=0.002, P=0.005); On the 14th and 28th days of treatment, the total effective rate of TCM efficacy in the treatment group was 75.00% and 94.44% respectively, and that in the control group was 45.16% and 64.52% respectively, and the treatment group was significantly better than the control group (P=0.018, P=0.005). Compared with before treatment, the TCM syndrome scores in both groups were significantly reduced on the 14th and 28th days (P＜0.01); The TCM syndrome scores in the treatment group were significantly lower than those in the control group at the same time points after treatment (P＜0.01). Compared with before treatment, the sensory and motor nerve conduction speeds of the peroneal and median nerves in the two groups at 14th and 28th days were significantly increased (P＜0.01); Comparing the two groups at the same time point after treatment, the sensory and motor nerve conduction velocity of the peroneal and median nerves in the treatment group was significantly better than that in the control group (P＜0.05, P＜0.01). Conclusion Xiaotan Tongluo Gel combined with mecobalamin tablets can effectively improve the peripheral neurotoxicity induced by chemotherapy, TCM syndrome scores, and the nerve conduction velocity.
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<p><b>OBJECTIVE</b>Traditional Chinese medicine (TCM) is regarded as an important treatment for gastric cancer patients, especially for those in advanced stage. To evaluate the effects of TCM treatment on gastric cancer patients, the authors performed a retrospective study to report the result of the integrated treatment of TCM with chemotherapy for stage IV non-surgical gastric cancer.</p><p><b>METHODS</b>In this study, 182 patients with stage IV and non-surgical gastric cancer were retrospectively analyzed to evaluate the effects of TCM integrated with chemotherapy. Among the 182 cases, 88 cases received integrated therapy consisting of TCM and chemotherapy, while 94 cases received chemotherapy alone. The overall survival and Karnofsky performance status (KPS) score were measured as the main outcome.</p><p><b>RESULTS</b>The median overall survival of the integrated therapy group and chemotherapy group were 16.9 and 10.5 months, respectively. The 1-, 3- and 5-year survival rates of integrated therapy group vs. chemotherapy group were 70% vs. 32%, 18% vs. 4%, and 11% vs. 0%, respectively. There was a significant difference between the two groups (χ= 42.244, P > 0.001). After six-month treatment, KPS scores of the integrated therapy group and the chemotherapy group were 75.00 ± 14.78 and 60.64 ± 21.39, respectively (P > 0.001). The Cox regression analysis showed that TCM treatment is a protective factor for patients' overall survival.</p><p><b>CONCLUSION</b>This study demonstrated that TCM integrated with chemotherapy may prolong overall survival and improve survival rate and life quality of patients with stage IV non-surgical gastric cancer.</p>
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Objective To investigate the effects of methylnitronitrosoguanidine (MNNG) on the malignant transformation of human gastric mucosa GES-1 cells and explore the possible molecular mechanism. Methods The GES-1 cells was treated by 9 different concentrations of MNNG for 24h, then removed MNNG and culture cell normally. The cell proliferation was detected by CCK-8 assay after 24h. The effects of MNNG on invasion and migration ability were detected by Transwell invasion and migration tests after 24h. The apoptosis was detected by Annexin V-FITC/PI FCM after 48h, and the expression levels of NF-κB p65 mRNA and protein were measured by real-time fluorescent quantitative PCR and Western blotting respectively. Results 2×10–4mol/L MNNG was chose for the induction of malignant transformation of GES-1 cells by the statistic analysis, 2×104mol/L MNNG could increase the proliferation, promote the invasion and migration, suppress the apoptosis of GES-1 cells (P<0.01). The expression levels of NF-κB p65 mRNA and protein were upregulated in GES-1 cells after treatment with MNNG (P<0.05). Conclusions MNNG can accelerate the proliferation, invasion and migration of GES-1 cells and inhibit apoptosis. This effect may be related to the activation of NFκB.
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<p><b>OBJECTIVE</b>To evaluate the impact of Jinlongshe Granule (, JLSG) on quality of life (QOL) of stage IV gastric cancer patients.</p><p><b>METHODS</b>This randomized, double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer. They were equally randomized into a JLSG group and a placebo group. Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine (CM) treatment based on syndrome differentiation. Patients in JLSG group received additional JLSG, and those in the placebo group received an additional placebo. In the JLSG group, 19 patients who completed the study were used for analysis. In the placebo group, finally the data of 20 patients who completed the study were used for analysis. The treatment course was at least 3 months, and the follow-up duration was at least 6 months in 5 interviews. Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared using different patient groups, changes over time and changes within one group over time independently to observe the tendency of changes in the scores.</p><p><b>RESULTS</b>Using time as the variant, there was signifificant difference in 4 functional scales (physical, role, emotional and social, P<0.05), 3 symptom scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and financial difficulties (P<0.05). There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Additional use of JLSG on the basis of routine CM treatment could improve the somatic function, role function, emotional function, social function, cognitive function and general QOL of patients with advanced gastric cancer, and relieve the symptoms of fatigue, nausea and vomiting, pain, loss of appetite and constipation.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Double-Blind Method , Drugs, Chinese Herbal , Therapeutic Uses , Placebos , Quality of Life , Stomach Neoplasms , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Weile Powder (WLP) on bicarbonate transporters in rats with gastric ulcers, and to probe its functional mechanisms.</p><p><b>METHODS</b>The 48 SD rats were randomly divided into the normal control group, the model group, the low dose WLP group (at the daily dose of 0.075 g/mL), the middle dose WLP group (at the daily dose of 0.150 g/mL), the high dose WLP group (at the daily dose of 0.030 g/mL), and the ranitidine group (at the daily dose of 0.030 g/mL), 8 in each group. The gastric ulcer rat model was prepared by the glacial acetic acid cauterization method. Rats in each medication group were administered from the 2nd day of modeling. Rats were sacrificed after 14-day successive medication. The protein was extracted from the ulcer tissue. The protein expressions of solute carrier26A3 (SLC26A3)and solute carrier26A6 (SLC26A6) were detected using Western blot. The gastric ulcer and its peripheral tissue were sectioned. The changes of cystic fibrosis transmembrane conductance regulator (CFTR) were measured by immunofluorescence.</p><p><b>RESULTS</b>Compared with the model control group, the expression levels of SLC26A3 increased in the high dose WLP group and the ranitidine group with statistical difference (P < 0.05). The expression levels of SLC26A6 increased in the high and middle dose WLP groups and the ranitidine group with statistical difference (P < 0.05). The expression level of CFTR also obviously increased in the high and middle dose WLP groups (P < 0.01).</p><p><b>CONCLUSION</b>WLP could elevate the expression levels of SLC26A6, SLC26A3, and CFTR, increase the secretion of bicarbonate, thus protecting the gastric mucosa.</p>
Subject(s)
Animals , Female , Male , Rats , Antiporters , Metabolism , Bicarbonates , Metabolism , Cystic Fibrosis Transmembrane Conductance Regulator , Metabolism , Drugs, Chinese Herbal , Pharmacology , Gastric Mucosa , Metabolism , Rats, Sprague-Dawley , Stomach Ulcer , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.</p><p><b>METHODS</b>An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups.</p><p><b>RESULTS</b>There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups.</p><p><b>CONCLUSIONS</b>TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".</p>