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Κυριακή 22 Αυγούστου 2021

The enhancement of Tetrandrine to gemcitabine-resistant PANC-1 cytochemical sensitivity involves the promotion of PI3K/Akt/mTOR-mediated apoptosis and AMPK-regulated autophagy

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Via histochem

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Acta Histochem. 2021 Aug 17;123(6):151769. doi: 10.1016/j.acthis.2021.151769. Online ahead of print.

ABSTRACT

BACKGROUND: In the process of tumor development, the resistance of pancreatic cancer cells to gemcitabine (GEM) is mainly due to the suppression and dysregulation of apoptosis signals to a large extent. Therefore, it is very necessary to develop pro-apoptotic drugs for combined treatment of pancreatic cancer to increase the activity of GEM and improve the prognosis o f pancreatic cancer.

METHODS AND RESULTS: GEM-resistant PANC-1 cells were treated with increasing doses of GEM. The effects of GEM and TET on apoptosis were evaluated by flow cytometry and Hoechst 33258 staining. We also evaluated the expression of survivin by real-time PCR, and the expression levels of proteins involved in apoptosis, autophagy, and PI3K/Akt/mTOR signaling were detected by western blotting. The results showed that TET downregulated expression of survivin by inhibiting the PI3K/Akt/mTOR signaling pathway to promote pancreatic cancer cell apoptosis, thereby enhancing pancreatic cancer cell sensitivity to GEM. Moreover, TET enhanced cytotoxic and autophagy-dependent cell death by upregulating the AMPK-autophagy axis, and this effect was reversed by inhibition of AMPK.

CONCLUSIONS: TET promotes apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway and promotes autophagy via up-regulating the AMPK signaling pathway to play an anti-tumor effect in GEM-re sistant pancreatic cancer cells, which represents a new therapeutic strategy for the treatment of GEM-resistant pancreatic cancer.

PMID:34416437 | DOI:10.1016/j.acthis.2021.151769

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