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Objective To explore the effect of KCNQ1OT1 gene knockout combined with bruceine D on the proliferation, migration, and invasion of breast cancer MDA-MB-231 cells. Methods Cell Counting Kit-8, wound healing, and Transwell invasion assay were used to detect the effects of bruceine D and siKCNQ1OT1 on the viability, migration, and invasion of MDA-MB-231 cells. Effect of bruceine D and siKCNQ1OT1 on the expression of KCNQ1OT1 in MDA-MB-231 cells was detected by qRT-PCR. Western blot was used to detect the effect of bruceine D and siKCNQ1OT1 on the expression of EMT-related proteins and CDC42, p-MKK7, MKK7 proteins in MDA-MB-231 cells. Results Bruceine D and siKCNQ1OT1 could significantly inhibit the viability, migration, and invasion of MDA-MB-231 cells, and the inhibitory effect was enhanced when they were combined (all P < 0.05); bruceine D downregulated the expression of KCNQ1OT1 in MDA-MB-231 cells (all P < 0.05); bruceine D combined with siKCNQ1OT1 significantly decreased CDC42, p-MKK7, N-cadherin, and Vimentin expression in MDA-MB-231 cells and increased the expression of E-cadherin (all P < 0.05). Conclusion Bruceine D combined with siKCNQ1OT1 significantly inhibit the proliferation, migration, invasion, and EMT of human breast cancer MDA-MB-231 cells, and its molecular mechanism may be related to the blocking of CDC42/MKK7 signaling pathway.
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Malignant tumors seriously threaten human life and health. Radiotherapy and chemotherapy are the conventional methods for the clinical treatment of advanced tumors. The prognosis and efficacy are still far from satisfactory due to the radiotherapy has serious adverse effects on the body and the chemotherapy often causes problems such as tumor resistance and cell proliferationinhibition. Therefore， the search for new， safe， and effective anti-tumor drugs and the elucidation of their molecular mechanisms are effective measures for clinical treatment of tumors and improvement of patients' quality of life. Active ingredients derived from Chinese herbal medicines and natural products have gradually become a hot spot in the research and development of anti-tumor drugs due to their multi-target and multi-channel anti-tumor pharmacological activity characteristics and their advantages such as less adverse reaction on the body. Bruceine D is a class of tetracyclic triterpenoids extracted from the fruit of the Chinese herbal medicine Bruceae Fructus， with anti-inflammatory， anti-malarial， anti-parasitic， and other pharmacological activities， and its anti-tumor activity is particularly significant. Pharmacological studies have found that bruceine D can regulate various cellular physiological activities such as proliferation， apoptosis， invasion， and migration of lung cancer， liver cancer， pancreatic cancer， intestinal cancer， and other cancer cells by targeting different signaling pathways. Bruceine D can be used in combination with other chemotherapeutic drugs to improve the sensitivity of tumor cells to chemotherapeutic drugs， thereby reducing the adverse effect of chemotherapy. Clinical application practice has shown that Bruceae Fructus oil emulsion injection containing bruceine D has significant advantages in the efficacy and safety of tumor treatment. Although there are many studies on the antitumor pharmacological activity of bruceine D and its clinical efficacy is significant， the specific antitumor molecular mechanism of bruceine D is still unclear， and there is a lack of systematic review on the existing antitumor mechanism of bruceine D. Therefore， based on the research on bruceine D in China and abroad in recent years， this paper reviewed the anti-tumor effect and related molecular mechanisms of bruceine D from six aspects， namely， tumor cell proliferation， apoptosis， metastasis and invasion， glucose metabolism process， autophagy， and chemotherapy sensitivity. This paper is expected to provide a pharmacological basis and scientific reference for the antitumor drug development and clinical application of bruceine D.
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Objective:To determine the clinical efficacy of selective decongestive devascularization of gastrosplenic (SDD-GSR) and splenectomy combined with pericardial vascularization in the treatment of portal hypertension in cirrhosis.Methods:A total of 134 patients with cirrhosis portal hypertension admitted to the First Affiliated Hospital of Wenzhou Medical University were enrolled in the study, including 102 males and 32 females, with an average age of 51 years. Of 61 cases of SDD-GSR were included in the SDD-GSR group, and 73 cases of splenectomy combined with pericardial vascularization were included in the control group. Preoperative and postoperative white blood cell count, platelet count, Child-Pugh grade of liver function, free portal pressure (FPP) and postoperation tomplication were analyzed in the two groups. Operation time, intraoperative blood loss, free portal pressure (FPP), Child-Pugh grade of liver function, preoperative and postoperative white blood cell count, platelet count, and postoperative complications were analyzedin the two groups.Results:The operation time and intraoperative blood loss of SDD-GSR group were 165 (110, 198) min and 280 (100, 650) ml, which were lower than those of control group [190 (135, 605) min and 895 (300, 3 500) ml], the differences were statistically significant ( P<0.05). Postoperative FPP of SDD-GSR group and control group was 39 (35, 44) cmH 2O (1 cmH 2O=0.098 kPa) and 38 (34, 44) cmH 2O, respectively, which were lower than those before operation, with statistical significance (both P<0.05). Postoperative platelet count and white blood cell count in SDD-GSR group were lower than those in control group, and the differences were statistically significant (all P<0.05). The Child-Pugh grading of recent postoperative liver function in SDD-GSR group was better than that in control group, with statistical significance ( P<0.05). The complication rate (abdominal infection and portal vein thrombosis) of control group was higher than SDD-GSR group. Conclusion:SDD-GSR is better than splenectomy combined with pericardial vascularization since it has less intraoperative bleeding, obvious improvement of liver function and fewer complications, and it may be an effective surgical option for the treatment of portal hypertension of cirrhosis.