Anemoside A3 activates TLR4-dependent M1-phenotype macrophage polarization to represses breast tumor growth and angiogenesis.

The polarization of macrophages has been previously demonstrated to be closely related to immune and inflammatory processes in the tumorigenesis and progression of breast cancer. In the present study, Anemoside A3 (A3), an active compound from Pulsatilla saponins, was screened out and polarized M0 macrophages into the classically activated macrophages (M1-phenotype). We found that A3 is an activator of TLR4/NF-κB/MAPK signaling pathway. A3 increased the expression of CD86+ (a marker of M1 macrophage) in M0 macrophage, and increased the typical M1 macrophage pro-inflammatory cytokines TNF-α, and IL-12 expression in a TLR4-dependent manner. A macrophage-cancer cell co-culture system was established to evaluate whether A3 can could switch tumor-associated macrophages (TAMs) to the M1-phenotype. In the co-culture system, A3 increased the expression of IL-12 in macrophages, whereby suppressing MCF-7 breast cancer cell line proliferation and VEGF-mediated angiogenesis. Moreover, A3 induced M1 macrophage polarization in the 4 T1 murine breast cancer model and effectively inhibited tumor growth and tumor angiogenesis. Collectively, these findings indicated that A3 induced M1 macrophages polarization to repress breast tumorigenesis via targeting the TLR4/NF-κB/MAPK signaling pathway. This study provides a rationale for utilizing traditional Chinese medicine extracts in the immunotherapy of breast cancer.

Short- And medium-term outcomes of reduced-port laparoscopic surgery in elderly patients with upper rectal cancer: A retrospective cohort study.

BACKGROUND: To investigate the short- and medium-term outcomes of using a reduced-port laparoscopic surgery (RPLS), compared to multi-port laparoscopic surgery (MPLS), for the treatment of upper rectal cancer (URC) among elderly patients. METHODS: We conducted a retrospective analysis of the clinical and follow-up data of 181 elderly patients with URC, who underwent radical laparoscopic surgery at our hospital, between January 2015 and January 2019. Among these 181 cases, 62 underwent RPLS and 119 MPLS. RESULTS: Compared to MPLS, RPLS decreased the length of surgical incision, lower pain on postoperative days 1 and 2, decreased the time to first flatus after surgery, as well as the time to mobilization after surgery. There was no difference between the short-term outcomes between the two laparoscopic approaches, and no difference in the 3-year disease-free and overall survival rate. CONCLUSION: Compared to MPLS, RPLS provides several advantages for the treatment of URC among elderly individuals, including a shorter length of surgical incision, reduced postoperative pain, shorter time to first flatus after surgery, earlier mobilization, and better cosmetic outcomes. These advantages are achieved with no difference in the length of surgery, nor in the 3-year disease-free and overall survival rate, compared to MPLS.

The synergistic antitumour effect of multi-components from Pulsatilla chinensis saponins in NCI-H460 lung cancer cell line through induction of apoptosis.

Context: Pulsatilla chinensis (Bunge) Regel (Ranunculaceae) possess antitumour effects; however, its antitumour potential has not been extensively investigated.Objective: To investigate the synergetic effect of multi-components from P. chinensis induced cell apoptosis and explore the mechanism.Materials and methods: The cytotoxicity was measured against NCI-H460, SMMC-7721, HCT-116 and U251 cell lines treated with eight monomers from P. chinensis. The synergetic effect of a combination of Pulsatilla saponin D (PSD), Raddeanoside R13 (R13), and Pulsatilla saponin A (PSA) was assessed using CalcuSyn3.0. Annexin V-FITC/PI and DAPI staining analyzed apoptosis of NCI-H460 cells treated with PSD, R13 and PSA alone or in combination. Proteins differential expression was analyzed using proteomic, DAVID Bioinformatics Resources, R software environment and KEGG database, and verified by western blotting.Results: PSD, R13, and PSA displayed greater antitumor activity with IC50 values of 5.6, 5.1 and 10.5 µM against NCI-H460 cells compared with other monomers. The combination of PSD, R13, and PSA had a synergistic effect at CI = 0.27 and induced 17.53% cells apoptotic detected by flow cytometric. Bioinformatic analysis showed an overview of the differentially expressed proteins and some signalling pathways. Moreover, some candidate proteins (LDHA, PI3K, NOL3 and cleaved-caspase-3) were validated by western blotting.Discussion and Conclusion: These results show PSD, R13, and PSA are good candidates as natural products for use in the treatment of lung cancer. Potential signalling pathways and protein targets need to be further validated. The application of the drug combination approach also provides a therapeutic strategy for cancer.