Isfahan University of Medical Sciences Journal of Isfahan Medical School 1027-7595 41 748 2024 01 21 Investigating the Simultaneous Effect of Oak Fruit Extract and Cisplatin on Cell Cycle, Apoptosis and, Expression of Key Genes P21, MMP2, CDK2 in Gastric Cancer Cell Line Investigating the Simultaneous Effect of Oak Fruit Extract and Cisplatin on Cell Cycle, Apoptosis and, Expression of Key Genes P21, MMP2, CDK2 in Gastric Cancer Cell Line 1128 1139 31139 10.48305/jims.v41.i748.1128 FA Maryam Mehdi Sasan Department of of Biology, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 0000-0002-1816-8210 Hamid Galehdari Department of of Biology, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 0000-0001-6281-4809 Seyed Mansour Seyed Nejad Department of of Biology, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran Salar Andarzi Department of of Biology, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 0000-0002-3502-709X Mohamad Reza Hajari Department of of Biology, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 0000-0002-8944-1464 Journal Article 2023 08 05 Background: The purpose of this research was to investigate the effect of oak fruit extract and its combination with chemotherapy drug cisplatin on AGS gastric adenocarcinoma cell line and also to evaluate its effect on cell cycle, apoptosis, and metastasis as well as the expression of key genes P21, CDK2, and MMP2. Methods: Cytotoxic effects of oak fruit extract and its combination with cisplatin on gastric cancer AGS cell line 48 hours after treatment were investigated using the MTT method. Using Real-Time PCR, the expression changes of P21, CDK2, and MMP2 genes were investigated. Cell cycle and apoptosis were also investigated by flow cytometry. Findings: The results showed that oak fruit extract combined with cisplatin causes more effects of apoptosis and cell death and inhibition of metastasis, as well as reducing the expression of MMP2 compared to the use of cisplatin alone after 48 hours of incubation. It also causes the cell cycle to stop in the Sub G1 phase and reduce the S phase. Also, the combination of these two substances has reduced the activity of CDK2/cyclin E by increasing the level of P21 protein. Conclusion: It seems that the combination of oak fruit extract and cisplatin can express genes that play a tumor suppressor role, such as P21, and reducing the expression of CDKs leads to growth inhibition. On the other hand, by reducing the expression of genes such as MMP2, it prevents cell migration. It also inhibits the growth of cancer cells by inducing apoptosis, and this effect is comparable to the effect of cisplatin alone. Background: The purpose of this research was to investigate the effect of oak fruit extract and its combination with chemotherapy drug cisplatin on AGS gastric adenocarcinoma cell line and also to evaluate its effect on cell cycle, apoptosis, and metastasis as well as the expression of key genes P21, CDK2, and MMP2. Methods: Cytotoxic effects of oak fruit extract and its combination with cisplatin on gastric cancer AGS cell line 48 hours after treatment were investigated using the MTT method. Using Real-Time PCR, the expression changes of P21, CDK2, and MMP2 genes were investigated. Cell cycle and apoptosis were also investigated by flow cytometry. Findings: The results showed that oak fruit extract combined with cisplatin causes more effects of apoptosis and cell death and inhibition of metastasis, as well as reducing the expression of MMP2 compared to the use of cisplatin alone after 48 hours of incubation. It also causes the cell cycle to stop in the Sub G1 phase and reduce the S phase. Also, the combination of these two substances has reduced the activity of CDK2/cyclin E by increasing the level of P21 protein. Conclusion: It seems that the combination of oak fruit extract and cisplatin can express genes that play a tumor suppressor role, such as P21, and reducing the expression of CDKs leads to growth inhibition. On the other hand, by reducing the expression of genes such as MMP2, it prevents cell migration. It also inhibits the growth of cancer cells by inducing apoptosis, and this effect is comparable to the effect of cisplatin alone.

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