人参皂苷Rh_2对胃癌细胞SGC7901/ADR耐药敏感性的影响
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摘要
目的观察人参皂苷Rh_2(G-Rh_2)对人胃癌SGC7901/ADR耐药细胞增殖、细胞周期及化疗敏感性的影响。方法 MTT法检测G-Rh_2与阿霉素(ADR)联用对SGC7901/ADR细胞增殖的影响,并计算逆转倍数(RF);流式细胞术检测G-Rh_2对SGC7901/ADR细胞周期的影响;蛋白印迹法检测G-Rh_2对SGC7901/ADR细胞P-糖蛋白(P-gp)、Bcl-2蛋白表达水平的影响。结果与ADR单药处理后细胞的半数抑制浓度(IC50)值(54.52μmol/L)比较,G-Rh_2与ADR联用时SGC7901/ADR细胞IC50值(30.14μmol/L)明显下降,RF为1.81;G-Rh_2与ADR联用能够将SGC7901/ADR细胞周期阻滞在G2/M期,与ADR单药处理比较,联用组细胞P-gp、Bcl-2的蛋白表达水平显著降低(P<0.05)。结论 G-Rh_2联合ADR能够提高SGC7901/ADR细胞的化疗敏感性,可能通过阻滞细胞周期、增加细胞凋亡进而抑制细胞增殖。
Objective To observe the effect of ginsenoside Rh_2(G-Rh_2) on the proliferation, cell cycle and chemotherapy sensitivity of human gastric cancer cell line SGC7901/ADR. Methods MTT assay was used to detected the effects of G-Rh_2 and adriamycin(ADR) on the proliferation of drug-resistant SGC7901/ADR cells and to calculate the reversal fold(RF). Flow cytometry was selected to detect The effects of G-Rh_2 on cell cycle. the effects of G-Rh_2 on the expression of P-gp and Bcl-2 proteins in drug-resistant SGC7901/ADR cells was detected by Western blotting. Results Compared with the IC50 value(54.52 μmol/L) after the ADR single drug treatment, the IC50 value(30.14 μmol/L) of the cells treated with G-Rh_2 and ADR decreased significantly, and RF was 1.81. G-Rh_2 combined with ADR arrested the cell cycle in G2/M phase and significantly decreased the protein expression of P-gp and Bcl-2(P < 0.05). Conclusion G-Rh_2 combined with ADR could increase the chemosensitivity of SGC7901/ADR cells, which may inhibit the proliferation of gastric cancer cells by blocking cell cycle and increasing apoptosis.
Objective To observe the effect of ginsenoside Rh_2(G-Rh_2) on the proliferation, cell cycle and chemotherapy sensitivity of human gastric cancer cell line SGC7901/ADR. Methods MTT assay was used to detected the effects of G-Rh_2 and adriamycin(ADR) on the proliferation of drug-resistant SGC7901/ADR cells and to calculate the reversal fold(RF). Flow cytometry was selected to detect The effects of G-Rh_2 on cell cycle. the effects of G-Rh_2 on the expression of P-gp and Bcl-2 proteins in drug-resistant SGC7901/ADR cells was detected by Western blotting. Results Compared with the IC50 value(54.52 μmol/L) after the ADR single drug treatment, the IC50 value(30.14 μmol/L) of the cells treated with G-Rh_2 and ADR decreased significantly, and RF was 1.81. G-Rh_2 combined with ADR arrested the cell cycle in G2/M phase and significantly decreased the protein expression of P-gp and Bcl-2(P < 0.05). Conclusion G-Rh_2 combined with ADR could increase the chemosensitivity of SGC7901/ADR cells, which may inhibit the proliferation of gastric cancer cells by blocking cell cycle and increasing apoptosis.
引文
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[21]周露婷,王翠翠,景洪标,等.Survivin和Bcl-2蛋白在胃癌细胞中的表达及其与化疗药物耐药性关系的研究[J].现代肿瘤医学,2014,22(7):1627-1629.
[2]Abraham J,Salama N N,Azab A K.The role of P-glycoprotein in drug resistance in multiple myeloma[J].Leuk Lymphoma,2015,56(1):26-33.
[3]Rocha G G,Sim?es M,Oliveira R R,et al.Effects of3β-acethyl tormentic acid(3ATA)on ABCC proteins activity[J].Int J Mol Sci,2012,13(6):6757-6771.
[4]Steffensen K D,Smoter M,Waldstrom M,et al.Resistance to first line platinum paclitaxel chemotherapy in serious epithelial ovarian cancer:The prediction value of ERCC1 and Tau expression[J].Int J Oncol,2014,44(5):1736-1744.
[5]Liu Y P,Ling Y,Qi Q F,et al.The effects of ERCC1expression levels on the chemosensitivity of gastric cancer cells to platinum agents and survival in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy[J].Oncol Lett,2013,5(3):935-942.
[6]Candelaria M,de la Cruz-Hernandez E,Taja-Chayeb L,etal.DNA Methylation-indenpendent reversion of gemcitabine resistance by hydralazine in cervical cancer cells[J].PLo S One,2012,7(3):e29181.
[7]Wang C,Hong Z,Chen Y.Involvement of p38 MAPK in the drug resistance of refractory epilepsy through the regulation multidrug resistance-assiociated protein 1[J].Neurochem Res,2015,40(7):1546-1553.
[8]Zhao Q,Li Y,Tan B B,et al.HIF-1 alpha induces multidrug resistance in gastric cancer cells by inducing Mia-27a[J].PLo S One,2015,10(8):e0132746.
[9]徐文,曹辉,杨远荣.人参皂苷Rh2的药理活性研究进展[J].中国医药导报,2017,14(28):42-45.
[10]Kim J H,Choi J S.Effect of ginsenoside Rh-2 via activation of caspase-3 and Bcl-2-insensitive pathway in ovarian cancer cells[J].Physiol Res,2016,65(6):1031-1037.
[11]徐晓军,石淑文,汤永民,等.人参皂苷Rh2抗白血病多药耐药细胞K562/VCR作用研究[J].中草药,2010,41(7):1131-1135.
[12]Zhang H,Gong J,Zhang H,et al.Induction of apoptosis and reversal of permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM by ginsenoside Rh2[J].Int J Clin Exp Pathol,2015,8(5):4444-4456.
[13]吴艳林,刘润田.人参皂苷Rh2对人肝癌细胞Hep-G2/ADM耐药逆转作用及其机制研究[J].医学研究生学报,2017,30(5):476-480.
[14]刘小霞,陈益,熊伟,等.人参皂苷Rh2通过自噬途径对KG1α细胞增殖和凋亡的影响[J].中草药,2017,48(2):305-311.
[15]高巧慧.桑黄发酵液总黄酮逆转SGC7901/ADR细胞多药耐药性研究[D].西安:陕西师范大学,2015.
[16]权恺,刘群,李萍,等.人参皂苷抗癌活性的最新研究进展[J].医学研究生学报,2015,28(4):427-431.
[17]Alakhova D Y,Kabanov A V.Pluronics and MDR reversal:An update[J].Mol Pharm,2014,11(8):2566-2578.
[18]Sui H,Fan Z Z,Li Q.Signal transduction pathways and transcriptional mechanisms of ABCB1/Pgp-mediated multiple drug resistance in human cancer cells[J].J Int Med Res,2012,40(2):426-435.
[19]Binkhathlan Z,Lavasanifar A.P-glycoprotein inhibition as a therapeutic approach for overcoming multidrug resistance in cancer:Current status and future perspectives[J].Curr Cancer Drug Targets,2013,13(3):326-346.
[20]Viedma-Rodríguez R,Baiza-Gutman L,SalamancaGómez F,et al.Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer(review)[J].Oncol Rep,2014,32(1):3-15.
[21]周露婷,王翠翠,景洪标,等.Survivin和Bcl-2蛋白在胃癌细胞中的表达及其与化疗药物耐药性关系的研究[J].现代肿瘤医学,2014,22(7):1627-1629.