Citri Reticulatae Pericarpium-Reynoutria japonica Houtt. herb pair suppresses breast cancer liver metastasis by targeting ECM1-mediated cholesterol biosynthesis pathway.

BACKGROUND: Liver metastasis is a frequent event in breast cancer that causes low survival rate and poor prognosis. Citri Reticulatae Pericarpium-Reynoutria japonica Houtt. (CR), a traditional Chinese herb pair, is used for the treatment of breast cancer liver metastasis or cholesterol gallstone disease in clinics. PURPOSE: This study attempted to investigate the potential therapeutic target and mechanism of CR herb pair on breast cancer liver metastasis. METHODS: The anti-metastatic and cholesterol-lowering activities of CR extract were evaluated in triple-negative breast cancer (TNBC) cell lines and an experimental liver metastasis model. The role of extracellular matrix protein 1 (ECM1) in the cholesterol biosynthesis pathway was determined by the knockdown and overexpression of ECM1 gene of TNBC cells. Changes in the gene and protein expression levels of ECM1 and the cholesterol biosynthesis pathway after CR treatment were detected in vitro and in vivo by real-time PCR and Western blot. RESULTS: The invasive and metastatic potentials and hypercholesterol levels of TNBC cells were positively associated with ECM1 expression. ECM1 knockdown reduced tumor cholesterol levels via downregulating cholesterol biosynthesis genes, including ACAT2, HMGCS1, HMGCR, MVK, and MVD, whereas ECM1 overexpression elicited the opposite effects. CR herb pair exerts the potential therapeutic effects on TNBC liver metastasis, which is partially mediated by disrupting ECM1-activated cholesterol biosynthesis process in TNBC cells. CONCLUSION: This study reveals that ECM1 is a novel target for the activation of cholesterol biosynthesis to promote TNBC liver metastasis occurrence. CR herb pair, an ECM1 inhibitor, maybe be considered to serve as an adjuvant therapeutic drug for liver metastasis in clinical practice.

Efficacy and safety of taxanes combined with chemotherapy drugs in advanced triple negative breast cancer: A meta-analysis of 26 randomized controlled trials.

Background: Researchers have demonstrated that the combined use of taxanes and chemotherapy drugs, especially paclitaxel-based treatment, appeared to clinically benefit on advanced triple negative breast cancer (TNBC). This meta-analysis aims to obtain the existent evidence on efficacy and safety for taxanes-based combination therapy to treat advanced TNBC. Methods: From 1991 to June 2022, seven databases (PubMed, Web of Science, Cochrane Library, Embase VIP, Wanfang, and CNKI databases) were comprehensively searched with no restricted language and region. The included randomized controlled trials (RCTs) compared taxanes-based combination therapy versus taxanes or other chemotherapy drugs. Statistical analysis was conducted using random-effect model, and the quality of RCTs was assessed using the tool of Cochrane Collaboration risk of bias. Results: Twenty-six RCTs with a total of 8,236 advanced TNBC patients were included. Compared with taxanes monotherapy, taxanes-based combination therapy significantly prolonged progression-free survival (HR=0.79, 95%CI=0.74-0.83, I2= 0.0%, p=0.000) and overall survival (HR=0.88, 95%CI=0.82-0.94, I2= 9.3%, p=0.000) and increased the risk of vomiting (RR=1.26, 95%CI=1.07-1.48) and diarrhea (RR=1.82, 95%CI=1.22-2.70, I2= 90.3%, p=0.003). No statistical differences were observed in complete response rate (CRR), objective response rate (ORR), disease control rate (DCR), and progressive disease (PD) indexes (CRR: RR=1.38, 95%CI=0.96-1.99; ORR: RR=1.20, 95%CI=0.73-1.98; DCR: RR=1.09, 95%CI=1.00-1.19; PD: RR=0.70, 95%CI=0.47-1.04). Compared with other chemotherapy drugs, taxanes plus other chemotherapy drugs significantly reduced the incidence of vomiting (RR=0.60, 95%CI=0.44-0.84, I2= 12.3%, p=0.002) and neutropenia (RR=0.58, 95%CI=0.35-0.96, I2= 73.0%, p=0.036) during the treatment period. Conclusions: Taxanes-based combination therapy is evidently effective and well-tolerated in advanced TNBC, indicating that it might be a recommended option for treating advanced TNBC patients to some extent. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022337802.

Effect of Yupingfeng granules on HA and Foxp3(+) Treg expression in patients with nasopharyngeal carcinoma.

OBJECTIVE: To investigate the effect of Yupingfeng on hyaluronic acid (HA) and Foxp3(+) Treg in patients with nasopharyngeal carcinoma. METHODS: A total of 58 cases of nasopharyngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum Foxp3(+) Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay. RESULTS: After radiotherapy and chemotherapy, the contents of Foxp3(+) Treg and HA were significantly decreased in two groups (P < 0.05), and the decrease of treatment group was more significantly (P < 0.01). Correlation analysis showed positive correlation between Foxp3(+) Treg and HA (P < 0.05). After treatment, the incidence of side effects in two groups was significantly decreased. And there was significant difference between two groups (P < 0.05). CONCLUSIONS: Combined chemotherapy and radiotherapy with Yupingfeng treatment can decrease the levels of Foxp3(+) Treg and HA in nasopharyngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.