Effects of Astragalin on apoptosis of undifferentiated gastric cancer cells

doi:10.12047/j.cjap.6259.2022.097

Abstract

Abstract: Objective: To investigate the effects and related molecular mechanisms of Astragalin on undifferentiated gastric cancer cell HGC-27. Methods: Astragalin was used to treat HGC-27 cells, the cell proliferation activity was detected by CCK-8 method, the cell morphology was observed under inverted microscope, hoechst 33342 and JC-1 staining were used to observe the changes of nucleus formation and mitochondrial membrane potential, the cell cycle and apoptosis rate were detected by flow cytometry, the reverse transcription level of the gene was analyzed by the second-generation sequencer. Results: Astragalin inhibited the proliferation of HGC-27 significantly (P＜0.01), down-regulated mitochondrial membrane potential, induced cell apoptosis, blocked the cell cycle in G1 prophase. At the same time, Astragalin up-regulated the transcription levels of genes bax and bad, down-regulated the transcription levels of genes egf, egfr, pik3cb, pdk1, akt3 and bcl-2. Western blot analysis also showed that the expressions of PI3K and Akt protein were decreased, and the proportion of Bax and BCL-2 protein was increased significantly (P＜0.01). Conclusion: The apoptosis of undifferentiated gastric cancer cell line HGC-27 can be induced by Astragalin through inhibition of EGFR/PDK/Akt signaling pathway, and the cell cycle can be blocked in G1 phase, which has a certain therapeutic effect on undifferentiated gastric cancer.

Key words: Astragalin, gastric cance, signaling pathway, cell apoptosis, cell culture

CLC Number:

R735.2

CHU Zhi-heng, HE Shi-yan, WANG Yu, ZHU Ruo-ting, GU Yi-ling, CHEN Jia-yu. Effects of Astragalin on apoptosis of undifferentiated gastric cancer cells[J]. CJAP, 2022, 38(5): 520-524.

References

[1] Chung HC, Bang YJ, Fuchs CS, et al. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811[J]. Future Oncol, 2021, 17(5): 491-501.
[2] 赵翔宇, 何振宇, 宰守峰. 人参皂苷Rg5对胃癌细胞周期和侵袭的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(1) : 51-55.
[3] Ishigami H, Yamaguchi H, Yamashita H, et al. Surgery after intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology findings[J]. Gastric Cancer, 2017, 20(1): 128-134.
[4] Kimura Y, Fujii M, Masuishi T, et al. Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC-06)[J]. Gastric Cancer, 2018, 21(3): 421-427.
[5] Liu L, Wang D, Qin Y, et al. Astragalin promotes osteoblastic differentiation in MC3T3-E1 cells and bone formation in vivo[J]. Front Endocrinol, 2019, 10: 228-238.
[6] Cid-Ortega S, Monroy-Rivera JA. Extraction of kaempferol and its glycosides using supercritical fluids from plant sources: A review[J]. Food Technol Biotech, 2018, 56(4): 480-493.
[7] Li W, Hao J, Zhang L, et al. Astragalin reduces hexokinase 2 through increasing miR-125b to inhibit the proliferation of hepatocellular carcinoma cells in vitro and in vivo[J]. J Agric Food Chem, 2017, 65(29): 5961-5972.
[8] Peng L, Gao X, Nie L, et al. Astragalin attenuates dextran sulfate sodium (DSS) -induced acute experimental colitis by alleviating gut microbiota dysbiosis and inhibiting NF-κB activation in mice[J]. Front Immunol, 2020, 11: 2058-2058.
[9] Guardiola S, Varese M, Sánchez-Navarro M, et al. A third shot at EGFR: New opportunities in cancer therapy[J]. Trends Pharmacol Sci, 2019, 40(12): 941-955.
[10] Lindner AU, Carberry S, Monsefi N, et al. Systems analysis of protein signatures predicting cetuximab responses in KRAS, NRAS, BRAF and PIK3CA wild-type patient-derived xenograft models of metastatic colorectal cancer[J]. Int J Cancer, 2020, 147 (10): 2891-2901.
[11] Lin JX, Xie XS, Weng XF, et al. UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expression of PDK1 through PI3K/AKT signaling[J]. J Exp Clin Canc Res, 2019, 38(1): 410-425.
[12] Scortegagna M, Lau E, Zhang T, et al. PDK1 and SGK3 contribute to the growth of BRAF-mutant melanomas and are potential therapeutic targets[J]. Cancer Res, 2015, 75(7): 1399-1412.
[13] Chen L, Yang L, Yao L, et al. Characterization of PIK3CA and PIK3R1 somatic mutations in Chinese breast cancer patients[J]. Nat commun, 2018, 9(1): 1-17.
[14] Zhang L, Li Y, Wang Q, Chen Z, et al. The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer[J]. Mol Cancer, 2020, 19(1): 10-27.
[15] Yip PY. Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway in non-small cell lung cancer[J]. Trans Lung Cancer Res, 2015, 4(2): 165-176.
[16] Wang X, Li G. MicroRNA-16 functions as a tumor-suppressor gene in oral squamous cell carcinoma by targeting AKT3 and BCL2L2[J]. J Cell Physiol, 2018, 233(12): 9447-9457.
[17] Glab JA, Cao Z, Puthalakath H. Bcl-2 family proteins, beyond the veil[J]. Int Rev Cel Mol Bio, 2020, 351: 1-22.
[18] Kalashnikova I, Mazar J, Neal CJ, et al. Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma[J].Nanoscale, 2017, 9(29): 10375-10387.