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Background: Esophageal cancer (EC) is a highly lethal malignancy with a grim prognosis and high mortality rates, primarily treated through surgery and radiotherapy. Herbal remedies are emerging as complementary approaches in cancer therapy. Here, we explore the potential therapeutic benefits of Chinese medicine raw Pinellia ternata (RP) in EC using web-based pharmacological methods and cellular experiments., Methods: The chemical components of RP were obtained by data mining via searches of the systematic pharmacology database, analysis platform, and literature on traditional Chinese medicine (TCM). The properties of the main components of RP were calculated using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The potential targets of the components were mined and collected through multiple databases, and the relevant potential targets of efficacy were imported into Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to obtain protein interactions. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment analysis of the potential targets were performed through Metascape. A target-pathway network was established using Cytoscape, and topological analysis was performed on the network so as to obtain the relevant targets and pathways of RP in the treatment of EC. The inhibitory effect of RP on human EC cells was verified by cell experiments., Results: Thirteen bioactive components of RP were screened, 87 related targets were obtained by construction, and 68 co-targets were obtained after taking intersection with EC related genes. The results of the protein-protein interaction (PPI) network analysis of the targets showed that the pharmacodynamic targets of hemicellulose might be closely related to the signaling pathways such as PI3K-Akt, FOS/JUN, and HIF-1. Meanwhile, GO and KEGG enrichment analysis showed that PI3K-Akt was also significantly enriched. The in vitro cellular experiments further indicated that raw hemicrania could inhibit EC through the PI3K-Akt signaling pathway., Conclusions: The pharmacodynamic mechanism of RP in the treatment of esophageal carcinoma was preliminarily revealed, which provided ideas and the basis for further experimental study of RP in the treatment of esophageal carcinoma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-684/coif). The authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Despite the success of small interfering RNAs (siRNAs) in clinical settings, their fast clearance and poor delivery efficiency to target cells still hinder their therapeutic effect. Herein, a new treatment system was constructed by combining thermosensitive liposomes with the macrophage membrane, tumor-targeting cyclic Arg-Gly-Asp peptide, a cell-penetrating peptide, and thermotherapy. The constructed system was found to be thermosensitive and stable; the proteins were inherited from the macrophage membrane. This new system combined with thermotherapy displayed the least uptake by macrophages, the greatest uptake by HepG2 cells, the most obvious HepG2 cell apoptosis, and the strongest inhibition of Bcl-2 mRNA and Bcl-2 protein in HepG2 cells. Moreover, 24 h after system administration in tumor-bearing mice, the most prominent distribution of siRNA was observed in tumors, while almost no siRNA was found in other organs. The strongest inhibition of Bcl-2 mRNA, Bcl-2 protein, and tumors was found in mice that had received the proposed system. In summary, when using the constructed system both in vitro and in mice, less uptake by the reticuloendothelial system, greater accumulation in tumor cells, and improved therapeutic efficacy were observed. Therefore, this new system can deliver siRNA selectively and efficiently, and it is a promising therapeutic candidate for precise tumor-targeted therapy., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Background: Epidermal growth factor receptor (EGFR) overexpression and mutations were existed in more than 40% of the lung cancer, and it's the one of molecular targets in clinical treatment. But the EGFR tyrosine kinase inhibitors (TKI)-resistance is becoming a challenging clinical problem as following the application of EGFR-TKIs, Gefitinib or Erlotinib. However, the mechanistic explanation for resistance in the some cases is still lacking. Here we researched the resistance mechanism of H1650 cells., Methods: Using real-time RT-PCR to analyze the EGFR mRNA expression level in EGFR wild-type non-small cell lung cancer (NSCLC) cells; MTT analysis detected the cytotoxicity for NSCLC cells to Erlotinib; Western blot analysis examined the mutant situations and the downstream signaling protein phosphorylation level in EGFR-mutant NSCLC cells with the treatment of Erlotinib or/and PI3K inhibitor, LY294002., Results: In the EGFR wild-type NSCLC cells, the expression level of EGFR mRNA varied dramatically and all the cells showed resistant to Erlotinib; In the EGFR-mutant cells, HCC827 and H1650 (the same activating-mutation type), HCC827 cells were Erlotinib-sensitive as well as H1650 demonstrated primary relative resistance. Western blot analysis showed the loss of PTEN and the p-AKT level was not inhibited with the treatment of Erlotinib or/and LY294002 in H1650 cells, while HCC827 cells were no PTEN loss and definitively decrease of p-AKT level., Conclusions: EGFR wild-type NSCLC cells were resistant to Erlotinib no matter of how EGFR mRNA expression level. EGFR-activating mutations correlated with responses to Erlotinib. The PTEN loss and activation of AKT signaling pathway contributed to Erlotinib resistance in EGFR-mutant NSCLC cell line H1650.