Objective To identify the blood-absorbed constituents of ethanol extract of Tetrastigma hemsleyanum (SYQ) and investigate its anti-breast cancer activity and underlying mechanisms. Methods Blood-absorbed components of SYQ were identified using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The effects of SYQ drug containing serum on proliferation and migration of 4T1 cells were evaluated by MTT, colony formation and wound-healing assays. A 4T1 tumor-bearing mouse model was established, control group, model group, cyclophosphamide (20 mg/kg) group, SYQ low-, medium-, and high-dose (5, 10, 20 g/kg) groups were set up. After drug intervention, ELISA was used to detect the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum. Hematoxylin-eosin (HE) staining was used to observe pathological changes in tumor tissue. Immunohistochemistry was used to detect CD68 and Ki67 expressions in tumor tissue. Western blotting was used to detect the expressions of TNF-α/protein kinase B (Akt)/signal transducer and activator of transcription 3 (STAT3) signaling axis and apoptosis related proteins in tumor tissues. Results A total of 19 blood components were identified by UHPLC-Q-TOF-MS/MS, mainly including flavonoids (rutin, tangeretin, narcissoside), phenylpropanoids, and other glycoside compounds (forsythoside E, darendoside B). The in vitro experimental results showed that SYQ drug containing serum significantly inhibited the proliferation, migration and colony formation of 4T1 cells (P < 0.01, 0.001). The in vivo experimental results showed that SYQ significantly inhibited tumor volume growth in tumor bearing mice (P < 0.001), with a tumor inhibition rate of 25.95% in high-dose group. SYQ reduced the levels of IL-6 and TNF-α in serum (P < 0.05, 0.001), induced tumor tissue necrosis and significantly reduced the expressions of CD68 and Ki67 (P < 0.001), while downregulated the expression levels of TNF-α, p-Akt/Akt, p-STAT3/STAT3 and B-cell lymphoma-2 (Bcl-2) in tumor tissue (P < 0.05, 0.01, 0.001). Conclusion SYQ could exerts anti-breast cancer effects by reducing the levels of inflammatory factors, inhibiting tumor cell proliferation and inducing tumor tissue necrosis. The mechanism may be related to the inhibition of TNF-α/Akt/STAT3 signaling axis.

Tetrastigma hemsleyanum Diels et Gilg  /  serum pharmacochemistry  /  breast cancer  /  inflammation  /  Akt/STAT3 signaling pathway  /  rutin  /  tangeretin  /  narcissoside  /  forsythoside E  /  darendoside B