Antitumor effect of antiplatelet agents in gastric cancer cells: an in vivo and in vitro study.
BACKGROUND
The antitumor effects of antiplatelet agents in gastric cancer cells are not well known. In this study, the possibility of gastric cancer treatment with an antiplatelet agent, mainly aspirin, was examined both in vivo and in vitro.


METHODS
For in vivo experiments, tumor-bearing mice were treated by an antiplatelet antibody or aspirin, and the tumor growth was compared. For in vitro experiments, human gastric cancer cell lines were used to confirm the cancer cell growth and inhibition by reducing the platelet count or using aspirin. We also examined several cytokines by using an ELISA assay and conducted microRNA microarray analysis of MKN-45 tumor cells to determine the influence of platelets or aspirin.


RESULTS
In vivo experiments showed that tumor growth was inhibited by halving the circulating platelet count by using an antiplatelet antibody or peroral daily aspirin. In vitro experiments showed that the proliferation rates of gastric cancer cell lines were increased after coincubation with platelets and that the effect was inhibited by aspirin. Although the expression of interleukin-6, platelet-derived growth factor, transforming growth factor-β, and prostaglandin E2 did not correlate with tumor growth inhibition by aspirin, seven microRNAs showed altered expression in cancer cells in response to coincubation with platelets or addition of aspirin. Cells transfected with mir-4670-5p showed a significant increase in proliferation compared to negative control cells.


CONCLUSIONS
Our study showed that platelets increased the proliferation of gastric cancer cells and that this increase was inhibited by antiplatelet antibody or aspirin. Mir-4670-5p may play an important role in these responses.
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Jota
J
Mikami
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan. ykurokawa@gesurg.med.osaka-u.ac.jp.
Yukinori
Y
Kurokawa
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Tsuyoshi
T
Takahashi
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Yasuhiro
Y
Miyazaki
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Makoto
M
Yamasaki
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Hiroshi
H
Miyata
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kiyokazu
K
Nakajima
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Shuji
S
Takiguchi
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Masaki
M
Mori
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Yuichiro
Y
Doki
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012844:Sincalide / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D035683:MicroRNAs; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D012844:Sincalide; D001241:Aspirin
Antiplatelet antibody; Aspirin; Mir-4670-5p; Platelet