Background: Breast cancer is the most prevalent female tumor, of which triple-negative breast cancer (TNBC) accounts for about 15%. Characterized by its aggressive nature and limited treatment options, TNBC currently stands as a significant clinical challenge. This study aimed to investigate the effects of icariin (ICA) on TNBC and explore the underlying molecular mechanism. Methods: Cell viability was assessed using CCK-8 assay, whereas the impact of ICA on cell proliferation was determined using colony formation assay and detection of proliferating cell nuclear antigen protein. Wound healing and transwell assays were used to evaluate the effects of ICA on cell migration and invasion, respectively. Flow cytometry was used to analyze cell cycle distribution and apoptosis. Transmission electron microscopy and monodansylcaverine staining were performed to detect the induction of autophagy, whereas molecular docking was conducted to predict the potential targets associated with autophagy. The in vivo anti-tumor effects of ICA were evaluated using a TNBC 4T1 xenograft mouse model. Protein expression levels were examined using immunoblotting and immunohistochemistry. Results: In vitro, ICA effectively suppressed the viability, proliferation, migration, and invasion of TNBC cells and induced G0/G1 phase cell cycle arrest, apoptosis, and autophagy in TNBC cells by regulating the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) signaling pathway. The knockdown of AMPK and inhibition of autophagy with 3-methyladenine reversed the effects of ICA, highlighting the importance of AMPK and autophagy in the anti-cancer mechanism of ICA. In vivo, ICA significantly inhibited TNBC growth, promoted autophagy, and regulated AMPK/mTOR/ULK1 pathway. Conclusions: Our findings demonstrated that ICA exerts anti-cancer effects against TNBC and the associated molecular mechanisms. This study will help to facilitate further preclinical and clinical investigations for the treatment of TNBC.

Purpose: Kanglaite injection (KLTi), made of Coix seed oil, has been shown to be effective in the treatment of numerous cancers. However, the anticancer mechanism requires further exploration. This study aimed to investigate the underlying anticancer mechanisms of KLTi in triple-negative breast cancer (TNBC) cells. Methods: Public databases were searched for active compounds in KLTi, their potential targets and TNBC-related targets. KLTi’s core targets and signaling pathways were determined through compound-target network, protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was carried out to predict the binding activity between active ingredients and key targets. In vitro experiments were conducted to further validate the predictions of network pharmacology. Results: Fourteen active components of KLTi were screened from the database. Fifty-three candidate therapeutic targets were selected, and bioinformatics analysis was performed to identify the top two active compounds and three core targets. GO and KEGG enrichment analyses indicated that KLTi exerts therapeutic effects on TNBC through the cell cycle pathway. Molecular docking results showed that the main compounds of KLTi exhibited good binding activity to key target proteins. Results from in vitro experiments showed that KLTi inhibited proliferation and migration of TNBC cell lines 231 and 468, induced apoptosis, blocked cells in the G2/M phase, downregulated the mRNA expression of seven G2/M phase-related genes cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2), and checkpoint kinase 1 (CHEK1), cell division cycle 25A (CDC25A), cell division cycle 25B (CDC25B), maternal embryonic leucine zipper kinase (MELK), and aurora kinase A (AURKA), as well as downregulated CDK1 protein expression and up-regulated protein expression of Phospho-CDK1. Conclusion: By utilizing network pharmacology, molecular docking, and in vitro experiments, KLTi was confirmed to have anti-TNBC effects by arresting cell cycle and inhibiting CDK1 dephosphorylation.

Resectable hepatocellular carcinoma (HCC) has poor prognosis because of its high recurrence rate. Immunotherapy has been tried for neoadjuvant therapy as it has shown excellent performance in the treatment of advanced HCC. This systematic review and meta-analysis aimed to assess the reported efficacy and safety of neoadjuvant immune checkpoint inhibitors (ICIs) for resectable HCC. Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify published and ongoing studies evaluating the efficacy and safety of neoadjuvant ICIs for resectable HCC up to October 2022. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Heterogeneity and subgroup analyses were performed, and data quality was assessed. The study was registered with PROSPERO (registration number: CRD42022371495). A total of 193 patients from 9 studies were included in this meta-analysis. The overall pathological complete response (pCR) rate was 12.9% (95%CI, 6.7–19.1%), and major pathological response (MPR) rate was 27.3% (95%CI, 15.1–39.4%), indicating a favorable association with neoadjuvant ICIs (pCR: OR = 0.17, p < 0.00001; MPR: OR = 0.38, p = 0.001). The pooled OR values for the incidence of grade 3 to 4 treatment-related adverse events and surgical delay rate were 0.26 and 0.05, respectively, which were significantly in favor of neoadjuvant ICIs (p < 0.0001; p < 0.00001, respectively). The subgroup analyses did not demonstrate superiority of one ICI over another ICI or combination therapy. The present study found that neoadjuvant ICIs were well tolerated by patients with resectable HCC and conferred therapeutic benefits in view of histopathological response results.

Background: Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate in the pathogenesis and development of multiple cancers and are aberrantly overexpressed in various types of cancer. This study aimed to develop a CTA-related gene signature (CTARSig) to predict prognosis in STAD patients and explore its underlying mechanisms.