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Signal transducer and activator of transcription 3 mediates apoptosis inhibition through reducing mitochondrial ROS and activating Bcl‐2 in gemcitabine‐resistant lung cancer A549 cells
Author(s) -
Liu JianSheng,
Yeh ChunAn,
Huang IChieh,
Huang GuanYu,
Chiu ChihHao,
Mahalakshmi B.,
Wen SuYing,
Huang ChihYang,
Kuo WeiWen
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30133
Subject(s) - gemcitabine , a549 cell , lung cancer , stat protein , apoptosis , stat3 , cancer research , adenocarcinoma , biology , cancer cell , cancer , medicine , oncology , biochemistry
Abstract Lung cancer is a leading cause of cancer‐related death worldwide. In this study, we used lung adenocarcinoma cells as a model, as lung adenocarcinoma has the highest mortality rate among all lung cancers. For the past few years, medical treatments or lung cancer have been limited because of chemotherapy resistance. Therefore, understanding the pathogenesis of the development of drug resistance in lung cancer is urgent. Gemcitabine is widely prescribed in the chemotherapeutic treatment of lung cancers. In this study, we developed gemcitabine‐resistant lung adenocarcinoma cells (A549‐GR) from the A549 cell line. The results showed that apoptotic protein expression and reactive oxygen species (ROS) generation were reduced in A549‐GR cells compared to A549 cells. Interestingly, we found that signal transducer and activator of transcription 3 (STAT3) translocated to the nucleus and mitochondria to affect the apoptotic pathway and ROS generation, respectively. Furthermore, treatment with STAT3 small interfering RNA diminished the increase in ROS production, proliferation and antiapoptotic proteins in A549‐GR cells. Taken together, the study demonstrated that STAT3 acts as an essential regulator and moderates apoptosis through two major mechanisms to induce gemcitabine resistance in cells; and these findings provide a potential target for the treatment of gemcitabine‐resistant lung cancer.

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