Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU
Gastric cancer (GC) is characterized by high tumor heterogeneity, increased surgical difficulty, and limited chemotherapy efficacy, and it is associated with a poor prognosis. The abnormal proliferation of cells involves abnormal activation of the PI3K/AKT/mTOR signaling pathway. Inhibition of this...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222301884X |
| _version_ | 1797364228345036800 |
|---|---|
| author | Ziyuan Zhong Tengkai Wang Ruochen Zang Yufei Zang Yaoyao Feng Shujun Yan Congcong Geng Na Zhu Qian Wang |
| author_facet | Ziyuan Zhong Tengkai Wang Ruochen Zang Yufei Zang Yaoyao Feng Shujun Yan Congcong Geng Na Zhu Qian Wang |
| author_sort | Ziyuan Zhong |
| collection | DOAJ |
| description | Gastric cancer (GC) is characterized by high tumor heterogeneity, increased surgical difficulty, and limited chemotherapy efficacy, and it is associated with a poor prognosis. The abnormal proliferation of cells involves abnormal activation of the PI3K/AKT/mTOR signaling pathway. Inhibition of this signaling pathway can inhibit tumor cell proliferation and induce cell apoptosis. This study evaluated the effect of PF-04979064, a dual inhibitor of PI3K and mTOR, on human GC cells. PF-04979064 significantly inhibited the proliferation of human gastric adenocarcinoma AGS cells and the undifferentiated GC cell line HGC-27, promoting cell apoptosis. Combination treatment with PF-04979064 and the GC first-line clinical drug 5-FU showed synergistic effects, and PF-04979064 markedly increased the sensitivity of GC cells to chemotherapy drugs. Western blot results showed that PF-04979064 significantly inhibited the PI3K/AKT/mTOR signaling pathway in GC cells, whereas RNA seq results demonstrated substantial alterations in gene expression profiles upon treatment with PF-04979064. This study provides insight into the effects of PF-04979064, thereby establishing a solid foundation for its potential clinical application in the treatment of GC. |
| first_indexed | 2024-03-08T16:33:14Z |
| format | Article |
| id | doaj.art-684f0cf7c27e4d9d8ddb63e702c3c32b |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-08T16:33:14Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-684f0cf7c27e4d9d8ddb63e702c3c32b2024-01-06T04:38:14ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-01-01170116086Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FUZiyuan Zhong0Tengkai Wang1Ruochen Zang2Yufei Zang3Yaoyao Feng4Shujun Yan5Congcong Geng6Na Zhu7Qian Wang8School of Medical Laboratory, WeiFang Medical University, No.7166, Baotong West Street, Weifang, Shandong, 261053, ChinaCheeloo College of Medicine, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong, 250012, China; Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, ChinaDepartment of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, ChinaCheeloo College of Medicine, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong, 250012, ChinaCheeloo College of Medicine, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong, 250012, ChinaDepartment of Clinical Laboratory, Qilu Hospital of Shandong University (Qingdao), 758 Hefei Road, Qingdao, Shandong, 266035, ChinaCheeloo College of Medicine, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong, 250012, ChinaDepartment of Clinical Laboratory, Qilu Hospital of Shandong University (Qingdao), 758 Hefei Road, Qingdao, Shandong, 266035, ChinaDepartment of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, China; Department of Clinical Laboratory, Qilu Hospital of Shandong University (Qingdao), 758 Hefei Road, Qingdao, Shandong, 266035, China; Corresponding author at: Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, China.Gastric cancer (GC) is characterized by high tumor heterogeneity, increased surgical difficulty, and limited chemotherapy efficacy, and it is associated with a poor prognosis. The abnormal proliferation of cells involves abnormal activation of the PI3K/AKT/mTOR signaling pathway. Inhibition of this signaling pathway can inhibit tumor cell proliferation and induce cell apoptosis. This study evaluated the effect of PF-04979064, a dual inhibitor of PI3K and mTOR, on human GC cells. PF-04979064 significantly inhibited the proliferation of human gastric adenocarcinoma AGS cells and the undifferentiated GC cell line HGC-27, promoting cell apoptosis. Combination treatment with PF-04979064 and the GC first-line clinical drug 5-FU showed synergistic effects, and PF-04979064 markedly increased the sensitivity of GC cells to chemotherapy drugs. Western blot results showed that PF-04979064 significantly inhibited the PI3K/AKT/mTOR signaling pathway in GC cells, whereas RNA seq results demonstrated substantial alterations in gene expression profiles upon treatment with PF-04979064. This study provides insight into the effects of PF-04979064, thereby establishing a solid foundation for its potential clinical application in the treatment of GC.http://www.sciencedirect.com/science/article/pii/S075333222301884XGastric cancerTargeted therapyCombination therapyProliferationApoptosis |
| spellingShingle | Ziyuan Zhong Tengkai Wang Ruochen Zang Yufei Zang Yaoyao Feng Shujun Yan Congcong Geng Na Zhu Qian Wang Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU Biomedicine & Pharmacotherapy Gastric cancer Targeted therapy Combination therapy Proliferation Apoptosis |
| title | Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU |
| title_full | Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU |
| title_fullStr | Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU |
| title_full_unstemmed | Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU |
| title_short | Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU |
| title_sort | dual pi3k mtor inhibitor pf 04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5 fu |
| topic | Gastric cancer Targeted therapy Combination therapy Proliferation Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S075333222301884X |
| work_keys_str_mv | AT ziyuanzhong dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu AT tengkaiwang dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu AT ruochenzang dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu AT yufeizang dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu AT yaoyaofeng dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu AT shujunyan dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu AT congconggeng dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu AT nazhu dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu AT qianwang dualpi3kmtorinhibitorpf04979064regulatestumorgrowthingastriccancerandenhancesdrugsensitivityofgastriccancercellsto5fu |