Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is closely related to tumour occurrence and development, oncogene expression, apoptosis inhibition and invasion and metastasis capacities. However, its function in the epithelial–mesenchymal transition (EMT) of pancreatic cancer is not fully understood. By comparing various wild-type pancreatic cancer cell lines, we determined which have a higher expression level of HNRNPA2B1 accompanied by the higher expression of N-cadherin and vimentin and lower expression of E-cadherin. Therefore, to elucidate the role of HNRNPA2B1 in EMT, we generated models of HNRNPA2B1 knockdown and overexpression in different types of pancreatic cancer cell lines (MIA Paca-2, PANC-1 and Patu-8988) and examined changes in expression of EMT-related factors, including CDH1, CDH2, vimentin and snail. The results show that HNRNPA2B1 promotes EMT development by down-regulating E-cadherin and up-regulating N-cadherin and vimentin, and also stimulates the invasion capacity and inhibits viability in human pancreatic cancer cell lines, the similar results in vivo experiments. Moreover, we found that HNRNPA2B1 likely regulates EMT progression in pancreatic carcinoma via the ERK/snail signalling pathway. The results of this work suggest that HNRNPA2B1 inhibition has potential antitumour effects, which warrants in-depth investigation.

Purpose: Patients are typically diagnosed with both hypertension and fibrosarcoma. Medical oncologists must prescribe suitable anti-hypertensive medications while considering anti-tumor drugs. Recently, immunotherapy has become prominent in cancer treatment. Nonetheless, it is unknown what role anti-hypertensive medications will play in immunotherapy. Methods: We examined the effects of six first-line anti-hypertensive medications on programmed cell death protein 1 antibody (PD1ab) in tumor treatment using a mouse model of subcutaneous fibrosarcoma. The drugs examined were verapamil, losartan, furosemide, spironolactone, captopril, and hydrochlorothiazide (HCTZ). The infiltration of CD8⁺ T cells was examined by immunohistochemistry. Additionally, several in vitro and in vivo assays were used to study the effects of HCTZ on human fibrosarcoma cancer cells to explore its mechanism. Results: Verapamil suppressed tumor growth and showed an improved effect on the tumor inhibition of PD1ab. Captopril did not affect tumor growth but brought an unexpected benefit to PD1ab treatment. In contrast, spironolactone and furosemide showed no effect on tumor growth but had an offset effect on the PD1ab therapy. Consequently, the survival time of mice was also significantly reduced. Notably, losartan and HCTZ, especially HCTZ, promoted tumor growth and weakened the effect of PD1ab treatment. Consistent results were observed in vivo and in vitro using the human fibrosarcoma cell line HT1080. We determined that the Solute Carrier Family 12 Member 3 (SLC12A3), a known target of HCTZ, may be the principal factor underlying its effect-enhancing properties through mechanism studies employing The Cancer Genome Atlas (TCGA) data and in vivo and in vitro assays. Conclusion: Verapamil and captopril potentiated the anti-tumor effect of PD1ab, whereas spironolactone and furosemide weakened the effect of PD1ab on tumor inhibition. Alarmingly, losartan and HCTZ promoted tumor growth and impaired the effect of PD1ab. Furthermore, we preliminarily found that HCTZ may promote tumor progression through SLC12A3. Based on this study, futher mechanism researches and clinical trials should be conducted in the future.

Pancreatic cancer remains one of the most lethal malignancies with limited therapeutic options. Luteolin, a natural flavonoid compound, has demonstrated po

Background and objective: Hepatocellular carcinoma (HCC) ranks among the most prevalent malignancies on a global scale. Stachyose (STA), an oligosaccharide widely present in legumes, has demonstrated various biological activities, including improving gut microbiota, anti-oxidative stress, and anti-tumor proliferation. This study aimed to predict potential targets of STA in HCC treatment and to identify key hub genes.Methods: By integrating multiple public databases and bioinformatics tools, we screened 34 candidate targets and constructed STA’s action network and PPI network in HCC. Functional enrichment analysis revealed 10 relevant KEGG pathways and key features related to cellular components, molecular functions, and biological processes. Finally, we conducted molecular docking, single gene analysis, and in vitro experimental validation on core targets.Results: Through screening of multiple databases, we identified 34 common targets associated with STA and HCC and subsequently constructed a protein-protein interaction (PPI) network. Through this analysis, we ultimately selected STAT3 and FN1 as core hub genes. Functional and pathway analyses indicated that these targets participate in multiple cancer-related pathways and have significant roles in cellular components, biological processes, and molecular functions. The results indicated a positive correlation between the expression of STAT3 and FN1 with angiogenesis, tumor inflammation, and epithelial-mesenchymal transition (EMT). Molecular docking experiments validated the stable binding capacity between STA and these core genes, and in vitro experiments further confirmed that STA could inhibit HCC cell proliferation and migration by downregulating STAT3 and FN1 expression.Conclusion: This study offers a comprehensive exploration of the molecular mechanisms through which STA may treat HCC, identifying STAT3 and FN1 as key targets and validating their clinical relevance and potential for application.

In this review, we outline the new expertise and research progress with luteolin as an antitumor agent, and clarify the related results from the aspects of tumor proliferation, apoptosis, invasion, metastasis, sensitivity to radiotherapy and chemotherapy, angiogenesis, and immunotherapy. In recent years, with the development of medical technology, the early detection rate of tumors has increased significantly. However, the number of cancer patients remains high. Therefore, a new and reasonably effective tumor therapeutic drug is urgently demanded. Luteolin, a flavonoid and widespread in nature, attracts more and more attention due to its universal biological utility, especially in the study of antitumor activity. This article reviews the work published in the past 20 years on the role and mechanism of luteolin as an antitumor agent, showing that this compound has a variety of effects for antitumor treatment by acting on different cytokines. Although clinical studies have not yet been widely carried out, a series of basic studies have confirmed that luteolin is a reasonably effective antineoplastic agent or anticancer adjuvant. Besides, derivatives of luteolin have good application prospects.

Osteosarcoma (OS) remains the most common bone tumor and the prognosis for many patients remains stagnant due to the unsatisfactory therapeutic effect of conventional treatment regimens. This research explored the effect and mechanism of a novel natural product, Eriocalyxin B (EB), in pathogenesis and immunotherapy in OS. Cell Count Kit 8 assay, colony formation assay, and wound healing assay were employed to detect the proliferative, colony-forming, and migratory abilities of human OS cells following EB treatment. Moreover, xenograft growth assay was performed to assess the effect of EB on OS in vivo. Subcutaneous OS models constructed in immunocompetent mice were employed to evaluate the effect of EB treatment in combination with immune checkpoint blockades (ICBs) PD1ab and CTLA4ab. Immunohistochemistry (IHC) staining was utilized to detect the level of CD8⁺ T cells infiltration and Ki67 expression. TARGET database, RNA interference technology, and qPCR assay were employed to explore the mechanism of EB on OS. EB inhibited the proliferative, colony-forming, and migratory abilities of the human OS cells MG63 and U2OS both in vitro and in vivo. TARGET data analysis demonstrated that up-regulation of TCEA3 was significantly negatively correlated with overall survival in OS patients. EB exerted anti-tumor activity via downregulation of TCEA3. EB, in conjunction with ICBs, synergistically optimized anti-tumorigenic activity against OS in immunocompetent mice. EB may promote infiltration of CD8⁺ T cells and down-regulate Ki67 expression. These results signaled that EB may have a role as a candidate therapeutic or preventive agent for the treatment of OS.