# Study on Autophagy Death of Alpha TC1 Clone 6 (αTC1-6) Cells Induced by Trametenolic Acid Through PI3K/AKT Pathway

## TL;DR

This study shows that Trametenolic Acid inhibits glucagon secretion and cell proliferation in pancreatic alpha cells by inducing autophagy through the PI3K/AKT pathway.

## Contribution

The study identifies Trametenolic Acid as a potential therapeutic agent for glucagonoma by inducing autophagy via the PI3K/AKT pathway.

## Key findings

- TA significantly inhibits αTC1-6 cell proliferation in a dose- and time-dependent manner.
- TA reduces glucagon secretion and induces autophagy in αTC1-6 cells.
- TA inhibits phosphorylation of PI3K, AKT, mTOR, and increases FoxO1 expression.

## Abstract

Glucagonoma, a rare neuroendocrine tumor, lacks targeted treatment drugs. Excessive secretion of glucagon is the main cause of its clinical syndrome. To explore targeted therapeutic drugs that can inhibit glucagon secretion and tumor proliferation, we investigated the effect of Trametenolic Acid (TA) on mouse pancreatic alpha TC1 clone 6 (αTC1-6) cells and its regulatory role in the PI3K/AKT signaling pathway. Cell viability of αTC1-6 cells was assessed via the MTT assay. Glucagon content in cell culture supernatants was measured using an Enzyme-Linked Immunosorbent Assay (ELISA). Autophagic vacuoles were visualized through Monodansylcadaverine (MDC) staining. The expression of autophagy-related proteins including Atg7, LC3 Ⅱ and PI3K/AKT signaling pathway-related proteins mTOR and FoxO1 were determined by Western blot. The results showed that the proliferation of αTC1-6 cells was significantly inhibited by TA in a dose- and time-dependent manner, and the IC50 was 140.71, 26.77 and 1.99 μM after treatment of 12, 24, and 48 h, respectively. The secretion of glucagon was significantly inhibited by TA. The MDC staining results showed that the fluorescent labeled autophagic vesicles in the TA group were increased. The Western blot results showed that the expression of Atg7 and LC3 Ⅱ was promoted by TA in a dose-dependent manner, the phosphorylation of PI3K, AKT, mTOR and FoxO1 was significantly inhibited, and the expression of FoxO1 protein was increased. These results demonstrated that TA can inhibit glucagon secretion, induce autophagy, and suppress cell proliferation in αTC1-6 cells. The mechanism may be associated with the PI3K/AKT signaling pathway.