中药药理与临床2025，Vol.41Issue(1)：45-51,7.
复方蜥蜴散调控PI3K/AKT/MMP通路对胃癌耐药细胞增殖、迁移及侵袭的影响
Compound Lizard Powder Regulates the PI3K/AKT/MMP Pathway to Inhibit the Proliferation,Migration,and Invasion of Cisplatin-Resistant Gastric Cancer Cells
摘要
Abstract
Objective:To observe the effects of Compound Lizard Powder on the proliferation,migration,invasion,and expression of resistance-re-lated proteins of cisplatin-resistant MKN45/DDP cells via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/matrix metallo-proteinase(MMP)signaling pathway.Methods:Forty SD rats were randomized into blank control and Compound Lizard Powder(17.2,34.4,and 68.8 g/kg)groups,with 10 rats in each group.The sera containing different doses of Compound Lizard Powder were then pre-pared.The CCK-8 method was used to detect the effects of Compound Lizard Powder(17.2,34.4,and 68.8 g/kg)-containing sera in single use and in combination with cisplatin on the proliferation of MKN45/DDP cells.The results showed that the serum containing Compound Liz-ard Powder administrated at 68.8 g/kg in single use and in combination with cisplatin had the best inhibitory effects,and thus it was used for the subsequent experiment.The subsequent experiment was designed with the following groups:blank control,cisplatin(1.2 μg/mL),20%serum containing Compound Lizard Powder,20%serum containing Compound Lizard Powder+cisplatin(1.2 μg/mL),and 20%serum containing Compound Lizard Powder+agonist 740Y-P(10 μmol/L).The proliferation,migration,and invasion of MKN45/DDP cells in each group were examined by the colony formation assay,scratch assay,and Transwell assay,respectively.Western blotting was employed to determine the expression levels of proteins in the PI3K/AKT/MMP signaling pathway,as well as resistance-related proteins such as multidrug resistance protein 6(MRP6)and P-glycoprotein(P-gp)in each group of cells.Results:The 20%sera containing Compound Lizard Powder administrated at 17.2,34.4,and 68.8 g/kg,as well as the combined therapy with cisplatin inhibited cell proliferation(P<0.05)in a dose-dependent manner.Compared with the blank control group and the cisplatin(1.2 μg/mL)group,the 20%serum containing Compound Liz-ard Powder,20%serum containing Compound Lizard Powder+cisplatin(1.2 μg/mL)and 20%serum containing Compound Lizard Powder+740Y-P(10 μmol/L)group inhibited the proliferation,migration,and invasion of MKN45/DDP cells(P<0.05,P<0.01),down-regula-ted the protein levels of MMP-2,MMP-9,Vimentin,P-PI3K,and P-AKT(P<0.05,P<0.01),and up-regulated the protein level of E-cadherin(P<0.01).Compared with the20%serum containing Compound Lizard Powder,the20%serum containing Compound Lizard Pow-der+cisplatin(1.2 μg/mL)inhibited the proliferation,migration,and invasion of cells(P<0.05,P<0.01),whilethe20%serumcontai-ning Compound Lizard Powder+740Y-P(10 μmol/L)showed reduced inhibitory effects(P<0.05,P<0.01),with up-regulated protein levels of MMP-2,MMP-9,Vimentin,P-PI3K,P-AKT,MRP6,and P-gp(P<0.05,P<0.01)and down-regulated protein level of E-cad-herin(P<0.01).Conclusion:Compound Lizard Powder may inhibit the proliferation,migration,and invasion of cisplating-resistant gastric cancer cells and suppress the expression of resistance-related proteins through the PI3K/AKT/MMP signaling pathway,thereby enhancing the cell sensitivity and reversing the cell resistance to cisplatin.关键词
复方蜥蜴散/胃癌顺铂耐药/增殖/迁移/侵袭/磷脂酰肌醇-3激酶/蛋白激酶/金属蛋白酶Key words
Compound Lizard Powder/Cisplatin resistance in gastric cancer/Proliferation/Migration/Invasion/PI3K/AKT/MMP引用本文复制引用
李铮,程翻娥,刘彩月,朱西杰,师小茜,李卫强..复方蜥蜴散调控PI3K/AKT/MMP通路对胃癌耐药细胞增殖、迁移及侵袭的影响[J].中药药理与临床,2025,41(1):45-51,7.基金项目
国家自然科学基金项目(编号:82260916) （编号:82260916）
宁夏医科大学科学研究资助项目(编号:XZ2023012) （编号:XZ2023012）
宁夏自然科学基金重点项目(编号:2021AAC02014). （编号:2021AAC02014）
