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
| Autor: | Chun-An Yeh, Guan-Yu Huang, B Mahalakshmi, I-Chieh Huang, Chih-Hao Chiu, Chih Yang Huang, Su-Ying Wen, Wei Wen Kuo, Jian-Sheng Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS STAT3 Transcription Factor Lung Neoplasms Physiology Clinical Biochemistry Apoptosis Deoxycytidine Models Biological 03 medical and health sciences 0302 clinical medicine Cytosol medicine Humans Lung cancer STAT3 A549 cell Cell Nucleus biology business.industry Cell Biology respiratory system medicine.disease Gemcitabine respiratory tract diseases Mitochondria Up-Regulation Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 A549 Cells Drug Resistance Neoplasm 030220 oncology & carcinogenesis STAT protein Cancer research biology.protein Adenocarcinoma business Reactive Oxygen Species medicine.drug |
| Zdroj: | Journal of cellular physiologyREFERENCES. 236(5) |
| ISSN: | 1097-4652 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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