ABSTRACT
Objective To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells. Methods AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR. Results Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated. Conclusion AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.
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Objective:To investigate the clinical efficacy and safety of Xiaoaiping injection combined with chemotherapy in treatment of non-small cell lung cancer (NSCLC) patients.Methods:Based on LinkDoc database, a total of 1 144 patients first diagnosed as stage Ⅲ B-Ⅳ NSCLC in 4 medical centers including Henan Cancer Hospital from 2014 to 2018 were enrolled. The baseline data of included patients was used to make propensity score matching. The patients were divided into the experimental group (Xiaoaiping injection combined with chemotherapy) and the control group (chemotherapy alone), 572 cases in each group. The objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), time to progression (TTP) and adverse reactions of the two groups were observed and compared. Results:Based on the statistical results of patients with records of efficacy evaluation, the ORR of the experimental group and the control group was 26.54% (86/324) and 26.07% (79/303), respectively, and there was no statistically significant difference ( χ2 = 0.02, P = 0.894); the DCR of both groups was 61.42% (199/324) and 62.38% (189/303), respectively, and there was no statistically significant difference ( χ2 = 0.06, P = 0.805). The median OS time of the experimental group and the control group was 21.2 months and 16.5 months, respectively, and there was a statistically significant difference ( χ2 = 7.53, P = 0.006). The median PFS time was 9.3 months and 8.9 months, respectively, and there was no statistically significant difference ( χ2 = 2.25, P = 0.134). The median TTP was 1.8 months (1.2 months, 5.1 months) and 1.7 months (1.2 months, 5.8 months), respectively, and there was a statistically significant difference ( Z = 3.89, P = 0.049). The incidence of bone marrow suppression was 75.52% (432/572) and 64.51% (369/572),respectively in the experimental group and the control group, and there was a statistically significant difference ( χ2 = 16.53, P <0.001); the incidence of liver dysfunction was 39.86% (228/572) and 29.55% (169/572), respectively, and there was a statistically significant difference ( χ2 = 13.43, P < 0.001); the incidence of abnormal kidney function was 2.45% (14/572) and 3.15% (18/572), respectively, and there was no statistically significant difference ( χ2 = 0.51, P = 0.473). Conclusions:Xiaoaiping injection combined with chemotherapy can prolong the survival time of patients with advanced NSCLC. It is necessary to pay attention to the potential risks of bone marrow suppression and liver damage.
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<p><b>OBJECTIVE</b>To explore the effect of downregulation of Tiam1 by siRNA on the esophageal squamous cell carcinoma (ESCC) EC9706 cells, and provide theoretical basis for gene therapy of ESCC using Tiam1 as a molecular target.</p><p><b>METHODS</b>Tiam1 siRNA was transfected into EC9706 cells, and expression changes of Tiam1 mRNA and protein after transfection were detected by quantitative real-time PCR and Western blotting. Cell proliferation was analyzed using CCK-8 kit. Cell cycle and apoptosis of the EC9706 cells were assessed by flow cytometry. Cell cycle-related proteins and cell apoptosis-associated proteins were analyzed by Western blotting.</p><p><b>RESULTS</b>Compared with the untreated group and control siRNA group, the relative expression levels of Tiam1 mRNA (1.00 and 0.11 ± 0.02) were not significantly different (P > 0.05). The relative expression levels of Tiam1 mRNA in the Tiam1 siRNA group at 24, 48 and 72 h after transfection were 0.30 ± 0.04, 0.09 ± 0.01 and 0.09 ± 0.006, respectively, significantly lower than that of the untreated group (P < 0.05 for all). The expression level of Tiam1 protein at 24 h after Tiam1 siRNA transfection in the EC9706 cells was 0.11 ± 0.02, significantly lower than that in the un-treated group (0.44 ± 0.05) and control siRNA group (0.44 ± 0.04, P < 0.05 for all). The percentages of G0/G1 cells in the Tiam1 siRNA group, untreated group and control siRNA group were (54.48 ± 2.14)%, (40.69 ± 1.85)% and (41.78 ± 1.31)%, respectively (P < 0.01). The percentages of S phase cells in the Tiam1 siRNA group, untreated group and control siRNA group were (27.18 ± 1.65)%, (32.32 ± 1.15)% and (30.35 ± 1.09)%, respectively (P < 0.01). The expression levels of cyclin D1 protein in the untreated group, control siRNA group and Tiam1 siRNA group were 0.43 ± 0.02, 0.41 ± 0.01 and 0.11 ± 0.02, respectively (P < 0.05). The expression levels of p27 protein in the untreated group, control siRNA group and Tiam1 siRNA group were 0.10 ± 0.01, 0.09 ± 0.02 and 0.20 ± 0.02, respectively (P < 0.05). The ratios of early apoptotic cells in the untreated group, control siRNA group and Tiam1 siRNA group were (10 ± 0.9)%, (10 ± 0.5)% and (27 ± 0.7)%, respectively (P < 0.01). The expression levels of Mcl-1 protein in EC9706 cells of untreated group, control siRNA group and Tiam1 siRNA group were 0.47 ± 0.12, 0.48 ± 0.13 and 0.16 ± 0.02, respectively (P < 0.05). The expression levels of Bcl-2 protein in EC9706 cells of the untreated group, control siRNA group and Tiam1 siRNA group were 0.49 ± 0.08, 0.50 ± 0.05 and 0.04 ± 0.03, respectively (P < 0.05). The caspase-3 activities in the untreated group, control siRNA group and Tiam1 siRNA group were 2.3 ± 0.09, 2.3 ± 0.10 and 16.0 ± 1.50, respectively; and that of caspase-9 were 2.3 ± 0.08, 2.3 ± 0.11 and 14.5 ± 0.9, respectively (P < 0.05 for all).</p><p><b>CONCLUSIONS</b>Tiam1 siRNA can significantly inhibit the proliferation of esophageal cancer EC9706 cells, induce cell cycle arrest and cell apoptosis. These effects are related to the regulation of the expressions of cell cycle-related genes (cyclin D1 and p27) and cell apoptosis-related genes (Mcl-1, Bcl-1, caspase-3 and caspase-9) by Tiam1 siRNA.</p>