# Exploring the impact of hAMSCs secretome on Panc1 cells via TNF-α/NF-κB (p50/p65)/Caspase 3 signaling pathways: An in vitro study

## TL;DR

This study shows that the secretome of human mesenchymal stem cells can trigger inflammation and cell death in pancreatic cancer cells.

## Contribution

The novel finding is that hAMSCs secretome simultaneously induces inflammation and apoptosis in Panc1 cells via TNF-α/NF-κB/Caspase 3 pathways.

## Key findings

- hAMSCs secretome up-regulates TNF-α, IL-1β, IL-8, and Caspase 3 in Panc1 cells.
- The secretome activates the NF-κB (p50/p65) pathway and induces apoptosis.
- These effects suggest potential for hAMSCs secretome in pancreatic cancer treatment.

## Abstract

The second most prevalent cause of mortality worldwide is cancer. Pancreatic cancer, known as the “king of cancers” due to its unfavorable prognosis and absence of symptoms, is among the fatal types of cancer. Despite the availability of various cancer therapy options, current strategies are often ineffective. Therefore, there is a constant need to explore novel platforms with low side effects and high efficacy. The application of stem cells or their derivatives in treating diseases including cancer, has become well-established. This study, focuses on investigating the effects of the secretome of human mesenchymal stem cells (hAMSCs) on Panc1 pancreatic cancer cells through the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB)/Caspase 3 signaling pathways. A co-culture system using 6-well plates transwell was utilized for this purpose. After 72 h, cell death in hAMSCs-treated Panc1 cells was analyzed through the TNF-α/NF-κB (p50/p65)/Caspase 3 signaling pathways using Western blot and enzyme-linked immunosorbent assay (ELISA). DAPI staining was used to visualize cell death in hAMSCs-treated Panc1 cells. The results showed an up-regulation of TNF-α, IL-1β, IL-8, p-IKK, p-IKKα, p-IKKβ, p-IκB, p53, PUMA, Caspase 3, and NF-κB (p50/p65) as well as a down-regulation of IKβ. These findings suggest that the secretome of hAMSCs promotes both inflammation and apoptosis in Panc1 pancreatic cancer cells simultaneously.

•Pancreatic cancer is a type of cancer with a high mortality rate worldwide.•Nowadays, stem cell therapy shows promise as a potential treatment option.•Secretome of stem cells activates TNF-α/NF-kB signaling pathway in Panc1 cells.•Secretome of stem cells induces expression of IL-8 and IL-1β in Panc1 cells.•Secretome of stem cells can induce apoptosis in Panc1 cells.

Pancreatic cancer is a type of cancer with a high mortality rate worldwide.

Nowadays, stem cell therapy shows promise as a potential treatment option.

Secretome of stem cells activates TNF-α/NF-kB signaling pathway in Panc1 cells.

Secretome of stem cells induces expression of IL-8 and IL-1β in Panc1 cells.

Secretome of stem cells can induce apoptosis in Panc1 cells.