Artemisinin liposomes regulates breast cancer metastasis and apoptosis through TIGIT/CD155 signal axis.

To investigate the mechanism of artemisinin liposomes regulating breast cancer metastasis and apoptosis through TIGIT/CD155 signal axis. Artemisinin liposomes were synthesized by thin film dispersion method and characterized in morphology, zeta potential, hydrodynamic size, entrapment efficiency as well as thermal stability. Furthermore, the cytotoxic effects of artemisinin liposomes on HC11 and 4T1 cell was evaluated by the MTS test. Scratch, transwell and colony formation experiment were conducted to assess the effect of artemisinin liposomes on cell metastasis. Apoptosis, cell cycle arrest were measured using flowcytometry. Meanwhile, bioinformatics analysis was used to investigate the relationship between TIGIT as a drug target for breast cancer and artemisinin liposomes, TIGIT/CD155 signal axis. Additionally, the mouse tumor model(group(saline, artemisinin, liposomes, artemisinin liposomes), dose(100 mg/kg/d)) was employed to detect the tumor-suppressive efficacy. Finally, the expression levels of Src, Akt, Mtor and Stat3 was further explored by Western Blot and RT-PCR to elucidate the regulatory mechanism of artemisinin liposomes on the TIGIT/CD155 signaling axis. The liposomes and artemisinin liposomes had average sizes of approximately 80 nm and 130 nm respectively, with a polydispersity index (PDI) of 0.225, 0.287. Artemisinin was effectively encapsulated within liposomes, as shown by the high encapsulation efficiency of 90.11% ± 0.88, with a cumulative release rate of 32.8% at pH = 5.5. In vitro studies demonstrated that artemisinin liposomes possessed significantly greater cytotoxicity against 4T1 cells, the IC50 values were approximately 480 µM. In contrast to artemisinin alone, artemisinin liposomes can effectively inhibit 4T1 cell metastasis, with an inhibition rate of 93.02% at 20 µM, and also promote cell apoptosis, with an apoptosis rate of 14.17% at 20 µM. Bioinformatic analysis demonstrated that TIGIT/CD155 signal axis was highly expressed in breast cancer and had poor prognosis. In vivo results revealed that artemisinin liposomes alone produced an anti-tumor effect comparable to the combination of TIGIT/CD155 and IL-15. Ultimately, artemisinin liposomes can regulate breast cancer progression by modulating the TIGIT/CD155 signaling axis and critical factors in the SRC pathway, specifically SRC, AKT, STAT3, and mTOR. The clinical treatment of breast cancer does not rely on the use of chemotherapy drugs alone, but selects the effective ingredients of Chinese medicine with higher safety.