Dahuang Zhechong Pill Combined with TNS4 Silencing Inhibits the NF-Κb/VEGF Pathway To Slow Down The Progression Of Pancreatic Cancer.

Abstract

Introduction: Pancreatic cancer (PC) is a highly aggressive malignancy with limited treatment options and poor prognosis. Dahuang Zhechong Pill, a traditional Chinese medicine, has shown promise in inhibiting inflammation. This study investigates the effects of combining Dahuang Zhechong Pill with TNS4 silencing on PC, focusing on their combined role in suppressing PC progression and exploring potential therapeutic applications. Intellectual property implications related to this combination are also explored.

Methods: Bioinformatic analysis was used to identify the key role of TNS4 in PC. CFPAC-1 PC cells were cultured and genetically modified using lentiviral transfection to stably knock down TNS4 expression. Cell proliferation was assessed using the CCK-8 assay, while cell migration and invasion capabilities were evaluated through Transwell assays. Colony formation and flow cytometry were performed to analyze clonogenic potential and cell cycle distribution, respectively. Apoptosis was assessed using tunel staining. Subcutaneous and orthotopic tumor models were established in nude mice to investigate the in vivo effects. Mice were treated with Dahuang Zhechong Pill by oral gavage. Immunohistochemistry and immunofluorescence were employed to detect the expression of key proteins involved in the NF-κB/VEGF pathway, including E-cadherin and Vimentin. ELISA was used to measure circulating IL-17 and amylase levels in mouse serum to test inflammation response.

Results: TNS4 was upregulated in PC and positively associated with PC progression. TNS4 silencing significantly reduced CFPAC-1 cell proliferation, migration, and invasion in vitro. Flow cytometry demonstrated an increase in G0/G1 phase arrest and apoptosis in the TNS4 silencing group. Subcutaneous models showed the anti-tumor effect of TNS4 silencing. Furthermore, Dahuang Zhechong Pill treatment, when combined with TNS4 knockdown, resulted in a marked decrease in tumor size in orthotopic models. Immunohistochemical analysis revealed reduced expression of NF-κB and VEGF in tumor tissues from the combination treatment group. ELISA results indicated lower levels of serum IL-17, and amylase and higher levels of insulin in combination-treated mice.

Discussion: We proposed an innovative therapeutic patent combining traditional Chinese medicine with targeted gene silencing to inhibit PC progression. By investigating the synergistic effects of TNS4 silencing and Dahuang Zhechong Pill in suppressing the NF-κB/VEGF signaling pathway, our findings highlighted a promising strategy that targets tumor proliferation and modulates the inflammatory microenvironment in PC.

Conclusion: Dahuang Zhechong Pill, in combination with TNS4 silencing, effectively inhibits the NF-κB/VEGF pathway and inflammation response, leading to reduced PC progression. These findings suggest a potential therapeutic approach for targeting PC through the combined use of traditional Chinese medicine and gene editing.