RESUMO
ObjectiveTo investigate the mechanism of Biejiajian Wan in the intervention of primary liver cancer based on long non-coding RNA SNHG5 （lncRNA SNHG5）/micro RNA-26a-5p （miRNA-26a-5p）/glycogen synthase kinase-3β （GSK-3β） signal axis. MethodDouble luciferase reporting assay was used to verify the targeted interaction between lncRNA SNHG5 and miRNA-26a-5p， miRNA-26a-5p， and GSK-3β in HepG2 cells. Nude-mouse transplanted tumor model of human HepG2 were established and randomly divided into model group， Biejiajian Wan low-dose group （0.5 g·kg-1）， medium-dose group （1.0 g·kg-1）， and high-dose group （2.0 g·kg-1）， and sorafenib group （100 mg·kg-1）， with 10 mice in each group. The mice were given intragastric administration of normal saline or drug for 28 days， and the tumor volume was measured at different time. Hematoxylin-eosin （HE） staining was used to observe the histological changes of tumors. The nucleic acid levels of lncRNA SNHG5， miRNA-26a-5p， GSK-3β， and β-catenin mPNA in tumor tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of GSK-3β and β-catenin in tumor tissue were detected by western blot. ResultCompared with the SNHG5-WT （wild type） + miRNA NC （negative control） group， the relative luciferase activities of the SNHG5-WT + miRNA-26a-5p mimic group were decreased （P<0.05）. Compared with the GSK-3β-WT + miRNA NC group， the relative luciferase activity of the GSK-3β-WT + miRNA-26a-5p mimic group was decreased （P<0.05）. Compared with the model group， the tumor volume of Biejiajian Wan low-dose， medium-dose， and high-dose groups was significantly decreased （P<0.05， P<0.01）. Compared with the model group， the cells in the tumor tissue of nude mice in each dose group of Biejiajian Wan were sparsely arranged with necrocytosis， which showed concentration-dependent changes. Compared with the model group， the expression levels of lncRNA SNHG5， GSK-3β， and β-catenin were decreased （P<0.05， P<0.01）， while the expression of miRNA-26a-5p was increased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. Compared with the model group， the protein expression levels of GSK-3β and β-catenin were decreased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. ConclusionBiejiajian Wan may affect the necrosis of liver cancer cells through lncRNA SNHG5/miRNA-26a-5p/GSK-3β signal axis and thus play an anti-tumor role. This research will provide more theoretical basis for the clinical application of Biejiajian Wan.
RESUMO
ObjectiveTo evaluate the efficacy and influencing factors of Biejiajianwan in the treatment of primary liver cancer based on real-world data of traditional Chinese medicine （TCM）. MethodClinical diagnosis and treatment data of patients with primary liver cancer admitted to five Grade-A tertiary hospitals in Henan Province from January 2015 to December 2020 were collected from the medical electronic database. The patients treated with Biejiajianwan for ≥30 days were assigned to the exposure group and those without treatment with Biejiajianwan or treated with Biejiajianwan for <30 days to the non-exposure group. The propensity score matching model was used to balance confounding factors between the two groups according to the 1∶1 genetic matching method. Kaplan-Meier method was used for survival analysis and survival curve plotting. Log-rank was used to test the difference in survival rate between the two groups. Univariate analysis of Biejiajianwan in the treatment of primary liver cancer was performed by Log-rank test combined with the Kaplan-Meier method. The factors with statistical significance （P<0.05） were combined with unbalanced factors by the propensity score matching model， and at the same time， clinical common sense and relevant prognostic factors by literature search were considered， which were subjected to multivariate analysis by Cox proportional hazards regression model. ResultA total of 2 207 electronic cases were collected，including 174 cases in the exposure group （Biejiajianwan group） and 2 033 cases in the non-exposure group. After propensity score matching， there were 174 cases in the exposure group and 174 cases in the non-exposure group. The Kaplan-Meier method was used for survival analysis on the matched data， and the Log-rank test results showed that the survival rate of patients with primary liver cancer in the Biejiajianwan group was higher than that in the control group （χ2=12.193， P<0.01）. Cox proportional hazards regression model analysis showed that the regression coefficient of Biejiajianwan was -0.916 4 with the hazard ratio （HR） ［95% confidence interval （CI）］=0.4 （0.239 5-0.668 0）， P<0.01， and the regression coefficient of radiofrequency ablation treatment was -0.976 5 with HR （95% CI）=0.376 6 （0.172 8-0.821 1， P<0.05）. Fibrinogen （FIB） abnormal regression coefficient was 0.481 4 with HR （95% CI）=1.618 4（1.022 0-2.562 9），P<0.05. ConclusionBiejiajianwan can prolong the survival period of patients with primary liver cancer. Radiofrequency ablation is an independent protective factor for Biejiajianwan in the treatment of primary liver cancer，while abnormal FIB are independent risk factors for Biejiajianwan in the treatment of primary liver cancer.