2. Academic Validation
  3. Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU

Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU

  • Biomed Pharmacother. 2024 Jan:170:116086. doi: 10.1016/j.biopha.2023.116086.
Ziyuan Zhong 1,  Tengkai Wang 2,  Ruochen Zang 3,  Yufei Zang 4,  Yaoyao Feng 4,  Shujun Yan 5,  Congcong Geng 4,  Na Zhu 5,  Qian Wang 6
Affiliations

Affiliations

  • 1 School of Medical Laboratory, WeiFang Medical University, No.7166, Baotong West Street, Weifang, Shandong, 261053, China.
  • 2 Cheeloo 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, China.
  • 3 Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, China.
  • 4 Cheeloo College of Medicine, Shandong University, No. 44 Wenhua West Road, Jinan, Shandong, 250012, China.
  • 5 Department of Clinical Laboratory, Qilu Hospital of Shandong University (Qingdao), 758 Hefei Road, Qingdao, Shandong, 266035, China.
  • 6 Department 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. Electronic address: wangqianqd@qiluhospital.com.
PMID: 38159377 DOI: 10.1016/j.biopha.2023.116086
Abstract

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.

Keywords

Apoptosis; Combination therapy; Gastric cancer; Proliferation; Targeted therapy.

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