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| Study on Mechanism of Total Flavonoids from Allium polyrhizum Promoting Apoptosis of Cervical Cancer Cells Through m6A-IGF2BP2 Dependent Pathway |
| ZHAO Cai-Quan, ZHAO Peng, TU Ya, BAI Li-Ge* |
| College of Ecology and Environment, Baotou Teachers' College, Baotou 014030, China |
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Abstract Cervical cancer (CC) is a gynecological malignancy, and most of the flavonoids have anti-cervical cancer activities. However, whether the total flavonoids of Allium polyrhizum also have anti-cervical cancer activity is rarely reported. Quantification of cell counting kit-8 (CCK-8) assay, scratch assay, flow cytometry, real-time quantitative PCR, immunoblotting, spot hybridization, N6-methyladenine (m6A), methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) methods were used to detect the growth of cervical cancer cells treated with total flavonoids of A. polyrhizum, and found that total flavonoids of A. polyrhizum had a significant effect on HeLa, SiHa and CaSki cervical cancer cells, which could effectively inhibit their proliferation and migration, and promote the apoptosis of HeLa cells. After treatment of HeLa cells with A. polyrhizum total flavonoids, the expression of a pro-apoptotic protein of B-cell lymphoma-2 associated X protein (BAX) was significantly up-regulated, and the high level of global m6A modification was related to significant downregulation of m6A demethylase fat mass and obesity-associated protein (FTO) expression. In addition, the expression of the m6A-reading protein insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was significantly increased. Bioinformatics prediction revealed that there was a high confidence m6A modification site on BAX mRNA, and IGF2BP2 also bound to this site. Similarly, both the m6A antibody and IGF2BP2 antibody could significantly enrich BAX mRNA. In conclusion, this study demonstrated that the total flavonoids of A. polyrhizum had good anti-cervical cancer activity and may played an anticancer role by promoting apoptosis of cervical cancer cells through the m6A-IGF2BP2 related molecular mechanism. Finally, the results of this study could provide a theoretical basis for the related research on the anti-tumor mechanism of flavonoids, as well as some theoretical reference for the development and application of novel drugs.
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Received: 01 April 2024
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Corresponding Authors:
* bailige2022@126.com
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