title: Evaluation of antagonistic effects of metformin with Cisplatin in gastric cancer cells.
abstract: Metformin has recently been introduced as an anti-cancer agent. In this study, we evaluated the effect of metformin and metformin/cisplatin on human gastric MKN-45 cell line. When we used metformin alone, it could inhibit proliferation and induce apoptosis, but it diminish anti-proliferative effects of cisplatin when they are used in combination. Further, we checked mRNA levels of survivin, mTOR, and Akt by real-time PCR. When MKN-45 cells were treated with metformin/cisplatin, the expression of survivin and mTOR were increased. The antagonistic effect of metformin on cisplatin could be through survivin and mTOR signaling pathways. Our results also suggest that interfering effect of metformin on cisplatin may be also through upregulation of Akt. Regarding the pivotal role of Akt in drug resistance, it may be reasonable to conclude that the antagonistic effect of metformin on cisplatin effect may be through this central mediator of drug resistance. Taken together, it seems that metformin is not a good option for sensitizing MKN-45 cell line to cisplatin, and in co-prescription of metformin and cisplatin in gastric cancer patients who suffer diabetes type 2, it should be highly cared.
authors: Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran ; Department of Biology, Faculty of Food Industry and Agriculture, Standard Research Institute (SRI), Karaj, Iran.
authors: Vahid
authors: V
authors: Lesan
authors: Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Seyed H
authors: SH
authors: Ghaffari
authors: Department of Basic Science, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors: Jamile
authors: J
authors: Salaramoli
authors: Stem Cell Preparation Unit, Eye Research Center, Farabi Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mansour
authors: M
authors: Heidari
authors: Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Masoumeh
authors: M
authors: Rostami
authors: Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Kamran
authors: K
authors: Alimoghaddam
authors: Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors: Ardeshir
authors: A
authors: Ghavamzadeh
keywords: Akt; Cisplatin; Gastric cancer; Metformin; Survivin; mTOR
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