Stapled anoplin peptide combined with photothermal therapy enhances oncolytic immunotherapy of triple-negative breast cancer / 中国中药杂志

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.

Effect of 6-Shogaol on invasion and migration of triple negative breast cancer cells via Hedgehog/Glil signaling pathway / 中国药理学通报

Aim To explore the effects of the expression of the transcription faetor Glil of Hedgehog ( Hh ) signaling pathway and the 6-Shogaol mediated Hedge- hog/Glil pathway on the proliferation, invasion and migration in MDA-MB-231 eells of triple negative breast eaneer.Methods MDA-MB-231 eells were transfected by lentiviral vectors to stably overexpressed Glil gene.The overexpression efficiency of Glil was verified by qRT-PCR and Western blot.CCK-8 and EdlJ assays were used to detect the effect of Glil expression and 6-Shogaol on cell viability.Cell scratch assay and Transwell assay were used to detect the ability of migration and invasion.Western blot was used to detect the proteins expression of Hedgehog signaling pathway and other related genes.Results MDA-MB- 231-Glil overexpression cell line was successfully established.When Gli 1 gene was overexpressed, the invasion and migration ability of cells was significantly improved, anrl the expression of Hh signaling pathway gene Glil , EMT marker gene Vimentin, Hippo signaling pathway genes YAP and TEAD4 inereased.When the expression of Glil was inhibited by the Hh/Gli pathway inhibitor Gant61 , the proliferation, invasion and migration abilities were suppressed.When the eells were treated with 6-Shogaol, the abilities of proliferation, invasion and migration were inhibited as well as the proteins expression of Glil , Vimentin, YAP and TEAD4 deereased.Conclusions Glil gene ean promote the invasion and migration of MDA-MB-231 eells.6-Shogaol ean inhibit proliferation, invasion and migration of breast eaneer eells through Hedgehog signaling pathway, suggesting that transcription factor Glil may be one of the targets of 6-Shogaol.