Mitochondrial transplantation inhibits cholangiocarcinoma cells growth by balancing oxidative stress tolerance through PTEN/PI3K/AKT signaling pathway

Superoxide Dismutase PTEN Phosphohydrolase Mice, Nude Apoptosis 3. Good health Mitochondria Cholangiocarcinoma Mice Phosphatidylinositol 3-Kinases Oxidative Stress Bile Ducts, Intrahepatic Bile Duct Neoplasms Cell Line, Tumor Animals Humans Proto-Oncogene Proteins c-akt Signal Transduction Cell Proliferation
DOI: 10.1016/j.tice.2023.102243 Publication Date: 2023-10-14T14:52:36Z
ABSTRACT
Cholangiocarcinoma (CCA) is a serious threat to human health, and tumor development is associated with abnormal mitochondrial function. It is believed that the introduction of healthy mitochondria into tumor cells can induce the oxidative stress in tumor cells to return to normal levels, thus exerting an inhibitory effect on tumor growth.Mitochondria isolated from 143BρW cells were co-cultured with HuCCT1 cells, and the mitochondria were stained with MitoTracker dye as a tracking label. Changes in apoptosis, proliferation, oxidative stress, and PTEN/PI3K/AKT signaling pathway were assessed. In addition, a CCA nude mouse transplantation tumor model was constructed to analyze the effects of mitochondrial transplantation on the above factors in nude mice. Furthermore, the expression of PTEN was interfered to observe the effect and mechanism of mitochondrial transplantation on the proliferation and apoptosis of CCA cells.Mitochondrial transplantation promoted apoptosis and inhibited cell proliferation in CCA cell line. SOD, GSH, and CAT activities were significantly increased, the expression of PTEN was activated, and the expression of p-PI3K and p-AKT were inhibited after mitochondrial transplantation. After mitochondrial transplantation + si-PTEN treatment, cell apoptosis, SOD, GSH, CAT activity, and the expression of PTEN were decreased, while the expression of p-PI3K and p-AKT were significantly enhanced.This study reveals the anti-tumor potential of mitochondrial transplantation through PTEN/PI3K/AKT signaling pathway to regulate cellular oxidative stress in CCA.
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