Transplantation of gastric epithelial mitochondria into human gastric cancer cells inhibits tumor growth and enhances chemosensitivity by reducing cancer stemness and modulating gastric cancer metabolism

被引：1

作者：

Tsai, Hsin-Yi ^{[1
,2
]}

Tsai, Kuen-Jang ^{[3
]}

Wu, Deng-Chyang ^{[4
,5
,6
]}

Huang, Yaw-Bin ^{[1
]}

Lin, Ming-Wei ^{[2
,6
,7
]}

机构：

[1] Kaohsiung Med Univ, Sch Pharm, Kaohsiung 80708, Taiwan

[2] I Shou Univ, Eda Hosp, Eda Canc Hosp, Dept Med Res, Kaohsiung 82445, Taiwan

[3] I Shou Univ, EDA Canc Hosp, Dept Surg, Kaohsiung 82445, Taiwan

[4] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Gastroenterol, Kaohsiung 80708, Taiwan

[5] Kaohsiung Med Univ, Coll Med, Dept Pediat, Kaohsiung 80708, Taiwan

[6] Kaohsiung Med Univ, Regenerat Med & Cell Therapy Res Ctr, Kaohsiung 80708, Taiwan

[7] I Shou Univ, Coll Med, Dept Nursing, Kaohsiung 82445, Taiwan

来源：

STEM CELL RESEARCH & THERAPY | 2025年 / 16卷 / 01期

关键词：

Gastric cancer; Mitochondrial transplantation; Cancer stemness; GRP78; Chemoresistance; Metabolism; Apoptosis; BREAST-CANCER; AEROBIC GLYCOLYSIS; POOR-PROGNOSIS; REPERFUSION;

D O I：

10.1186/s13287-025-04223-7

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

BackgroundGastric cancer is the malignant disease. The problems associated with cancer stemness and chemotherapy resistance in gastric cancer therapy remain unresolved. Glucose-regulated protein 78 (GRP78) is a biomarker of gastric cancer and modulates cancer stemness and chemoresistance. Previous studies have shown that mitochondrial transplantation from healthy cells is a promising method for treating various diseases and that the regulation of mitochondrial metabolism is crucial for modulating the stemness and chemoresistance of cancer cells. The aim of this study was to investigate the therapeutic effect of mitochondrial transplantation from normal gastric epithelial cells into gastric cancer and the associated mechanisms.MethodsThe expression of cancer stemness markers, intracellular oxidative stress, or apoptotic-related proteins were evaluated via flow cytometry. Western blotting was used to investigate the molecular mechanism involved in MKN45 or AGS human gastric cancer cells after transplantation with human gastric epithelial mitochondria. The mitochondrial metabolic function of gastric cancer cells was determined via a Seahorse bioanalyzer, and extracellular lactate was evaluated via bioluminescent assay. The viability of 5-fluorouracil (5-FU)-treated gastric cancer cells was detected via a CCK-8 assay. Furthermore, a xenograft tumor animal study was performed to validate the therapeutic effects of human gastric epithelial mitochondrial transplantation in gastric cancer. Immunohistochemistry and Western blotting were then used to assess the expressions related to cancer stemness and mitochondrial metabolism-related proteins in tumor tissues.ResultsTransplanting human gastric epithelial mitochondria downregulates gastric cancer mitochondrial biogenesis, glycolysis, GRP78-mediated cancer stemness, and increases oxidative stress, cell apoptosis under hypoxic conditions and chemosensitivity in response to 5-FU treatment. Moreover, the transplantation of epithelial mitochondria into gastric tumors inhibited the tumor growth in vivo tumor graft animal models. Therefore, mitochondrial transplantation can be considered for the treatment of gastric cancer.

引用

页数：17

共 75 条

[11] Mitochondrial transplantation strategies in multifaceted induction of cancer cell death [J].

Cruz-Gregorio, Alfredo ;

Aranda-Rivera, Ana Karina ;

Amador-Martinez, Isabel ;

Maycotte, Paola .

LIFE SCIENCES, 2023, 332

[12] Mitochondria-derived cell-to-cell communication [J].

Dache, Zahra Al Amir ;

Thierry, Alain R. .

CELL REPORTS, 2023, 42 (07)

[13]

Doulamis IP, 2021, METHODS MOL BIOL, V2277, P15, DOI 10.1007/978-1-0716-1270-5_2

[14] Monocarboxylate Transporters 1 and 4 and MTCO1 in Gastric Cancer [J].

Eskuri, Maarit ;

Kemi, Niko ;

Kauppila, Joonas H. .

CANCERS, 2021, 13 (09)

[15] CD44ICD promotes breast cancer stemness via PFKFB4-mediated glucose metabolism [J].

Gao, Ruifang ;

Li, Dan ;

Xun, Jing ;

Zhou, Wei ;

Li, Jun ;

Wang, Juan ;

Liu, Chen ;

Li, Xiru ;

Shen, Wenzhi ;

Qiao, Huan ;

Stupack, Dwayne G. ;

Luo, Na .

THERANOSTICS, 2018, 8 (22) :6248-6262

[16] Helicobacter pylori CagA Protein Attenuates 5-Fu Sensitivity of Gastric Cancer Cells Through Upregulating Cellular Glucose Metabolism [J].

Gao, Sujie ;

Song, Defeng ;

Liu, Yiting ;

Yan, Hongwei ;

Chen, Xuebo .

ONCOTARGETS AND THERAPY, 2020, 13 :6339-6349

[17] SIK2 promotes reprogramming of glucose metabolism through PI3K/AKT/HIF-1α pathway and Drp1-mediated mitochondrial fission in ovarian cancer [J].

Gao, Tian ;

Zhang, Xiaohong ;

Zhao, Jing ;

Zhou, Feng ;

Wang, Yaya ;

Zhao, Zheng ;

Xing, Jinliang ;

Chen, Biliang ;

Li, Jibin ;

Liu, Shujuan .

CANCER LETTERS, 2020, 469 :89-101

[18] Mitochondrial fission causes cisplatin resistance under hypoxic conditions via ROS in ovarian cancer cells [J].

Han, Youngjin ;

Kim, Boyun ;

Cho, Untack ;

Park, In Sil ;

Kim, Se Ik ;

Dhanasekaran, Danny N. ;

Tsang, Benjamin K. ;

Song, Yong Sang .

ONCOGENE, 2019, 38 (45) :7089-7105

[19] Transfer of mitochondria from astrocytes to neurons after stroke [J].

Hayakawa, Kazuhide ;

Esposito, Elga ;

Wang, Xiaohua ;

Terasaki, Yasukazu ;

Liu, Yi ;

Xing, Changhong ;

Ji, Xunming ;

Lo, Eng H. .

NATURE, 2016, 535 (7613) :551-+

[20] SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer [J].

Huang, Shimiao ;

Wang, Xuan ;

Zhu, Yin ;

Wang, Yadong ;

Chen, Jiaxuan ;

Zheng, Haoxuan .

CELL DEATH & DISEASE, 2023, 14 (12) :791

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