Curcumin regulates the miR-21/PTEN/Akt pathway and acts in synergy with PD98059 to induce apoptosis of human gastric cancer MGC-803 cells

  • J Int Med Res. 2019 Mar;47(3):1288-1297. doi: 10.1177/0300060518822213.
Zhanrong Qiang  1  2  3  4 ,  Lingyu Meng  3  5  4 ,  Caixia Yi  5 ,  Lianying Yu  1  2 ,  Wenxia Chen  1  2 ,  Weihong Sha  1  2
Affiliations
  • 1. 1 Southern Medical University, Guangzhou, Guangdong Province, China.
  • 2. 2 Department of Gastroenterology and Hepatology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.
  • 3. 3 Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Province, China.
  • 4. *These authors contributed equally to this work.
  • 5. 4 Guilin Medical University, Guilin, Guangxi Province, China.
PMID: 30727807 DOI: 10.1177/0300060518822213
Abstract

Objective: PD98059 is a potent and selective inhibitor of mitogen-activated protein kinase. Substantial preclinical evidence has shown an anti-tumor effect of curcumin on various solid tumors. This study aimed to investigate whether curcumin synergistically acts with PD98059 in exerting anti-gastric Cancer effects.

Methods: The cell counting kit-8 assay was used to detect cell proliferation of the human gastric Cancer MGC-803 cell line. Flow cytometry was performed to detect Apoptosis. Western blotting was used to detect Phosphatase and tensin homolog (PTEN) and phosphorylated Akt (p-Akt) expression levels. Quantitative reverse transcription-polymerase chain reaction was used to determine microRNA-21 (miR-21).

Results: A dose of 5 to 40 µM curcumin inhibited proliferation of MGC-803 cells in a dose- and time-dependent manner. A high dose of curcumin strongly inhibited p-Akt protein expression. With increasing curcumin levels, PTEN expression increased and miR-21 levels decreased. These results suggest that curcumin negatively modulated the miR-21/PTEN/Akt pathway. Moreover, after pretreatment with PD98059, cell Apoptosis induced by curcumin was significantly increased. Additionally, the inhibitory effects of curcumin on the miR-21/PTEN/Akt pathway were significantly enhanced.

Conclusion: PD98059 combined with curcumin may be a potential strategy for managing gastric Cancer.

Keywords
Curcumin; apoptosis; microRNA-21 (miR-21); mitogen-activated protein kinase (MAPK) inhibitor; phosphatase and tensin homolog (PTEN); stomach neoplasm.
Products