Abstract:Objective: To investigate the effect of β-carboline alkaloids extracted from Peganum harmala L. on the expression of FAK, PI3K, AKT, mTOR, Bcl-2 and Bax in transplanted tumor tissue of human gastric cancer SGC-7901 mice. Methods: The transplanted tumor model was established in mice. 50 Kunming mice were randomly divided into 5 groups: blank control group, 5-fluorouracil group, low-, medium-and high-dose β-carboline alkaloids groups, with 10 mice in each group. The tumor inhibition rate was calculated, the pathological changes of tumor tissues were detected by HE staining, the apoptosis of tumor cells was detected by TUNEL method, the mRNA expression of FAK, PI3K, Akt, mTOR, Bcl-2 and Bax were detected by RT-PCR The expression of FAK, PI3K, Akt, mTOR, Bcl-2 and Bax were detected by blot and immunohistochemistry. Results: The middle and high dose of β-carboline alkaloids can inhibit the growth of SGC-7901 mice tumor and reduce the tumor weight (P<0.01), which is better than the low dose of β-carboline alkaloids (P<0.05). He staining and TUNEL results showed that β-carboline alkaloids could damage the gastric tumor cells and induce apoptosis. RT-PCR, Western blot and immunohistochemistry showed that the middle and high doses of β-carboline alkaloids could significantly reduce the expression of FAK, PI3K, AKT, mTOR and Bcl-2 protein (P<0.01), and increase the expression of Bax protein (P<0.01), which was better than the low doses of β-carboline alkaloids (P<0.05) and the difference was statistically significant. Conclusion: The inhibitory effect of β-carboline alkaloids on gastric cancer is related to the decrease of Bcl-2, FAK, PI3K, AKT, mTOR protein expression and the increase of Bax protein expression, which indicates that β-carboline alkaloids may be a potential therapeutic drug for gastric cancer.
[1] 左婷婷,郑荣寿,曾红梅,等.中国胃癌流行病学现状[J].中国肿瘤临床,2017,44(1):52~58. [2] Fan Y, Patima A, Chen Y, et al. Cytotoxic effects of β-carboline alkaloids on human gastric cancer SGC-7901 cells[J].Int Clin Exp Med,2015,8(8): 12977~12982. [3] 樊玉祥,韩婧雅,张洪亮.β咔啉类生物碱对人胃癌SGC-7901小鼠移植瘤生长及凋亡相关蛋白表达的影响[J].新疆中医药,2017,35(4):3~6. [4] 冀娇娇,董洁,王加利,等.去氢骆驼蓬碱脂质体对人宫颈癌Hela细胞增殖作用研究[J].中国现代中药,2016,18(2):148~150,155. [5] 陈豫,帕提玛·阿布力米提,李凯,等.β-咔啉类生物碱对人胃癌SGC-7901细胞凋亡及PTEN、ERKmRNA表达的影响[J].新疆医科大学学报,2015,38(2):190~192,196. [6] 李芳,李玉凤,张景华.微小RNA通过调控肿瘤血管形成影响肿瘤转移[J].基因组学与应用生物学,2015,34(11):2332~2337. [7] Zhang XS, Hu YH, Gao HY, et al. Downregulation of Notch1 inhibits the invasion and metastasis of human gastric cancer cells SGC7901 and MKN74 in vitro through PTEN activation and dephosphorylation of Akt and FAK[J].Mol Med Rep,2017,16(2): 2318~2324. [8] Costa R, Han HS, Gradishar WJ. Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review[J].Breast Cancer Res Treat,2018,169(3): 397~406. [9] Magrys A, Bogut A, Kietbus M, et al. The role of the PI3K/mTOR signaling pathway in Staphylococcus epidermidis small colony variants intracellular survival[J].Immunol Invest,2018,47(3): 251~263. [10] 念家云,王笑民,富琦,等.基于PI3K/Akt/mTOR信号传导通路的抗癌中药单体的研究概况[J].中国药房,2019,(20):2870~2875.