人参皂苷CK对MCF-7细胞增殖、凋亡、上皮间质转化、PI3K/Akt信号通路的影响
|
摘要
目的探讨人参皂苷CK对人乳腺癌MCF-7细胞增殖、凋亡、上皮间质转化、PI3K/Akt信号通路的影响。方法 MCF-7细胞经不同浓度的人参皂苷CK处理后,MTT法检测细胞增殖,流式细胞术检测细胞凋亡,real-time q PCR法检测E-钙黏蛋白、N-钙黏蛋白、波形蛋白mRNA表达,Western blot法检测p-PI3K、p-Akt蛋白表达。结果与对照组比较,10μmol/L人参皂苷CK处理72 h,20、40、80μmol/L人参皂苷CK处理24、48、72 h后,对细胞增殖的抑制率显著增加(P<0.05);20、40、80μmol/L人参皂苷CK处理48 h后,细胞凋亡率和E-钙黏蛋白mRNA表达显著增加(P<0.05);20、40、80μmol/L人参皂苷CK处理48 h后,N-钙黏蛋白、波形蛋白mRNA表达,以及p-PI3K、p-Akt蛋白表达显著降低(P<0.05)。结论人参皂苷CK可抑制MCF-7细胞增殖、上皮间质转化,并诱导细胞凋亡,这可能与抑制PI3K/Akt信号通路相关。
AIM To explore the effects of ginsenoside CK on the proliferation,apoptosis,epithelial-mesenchymal transition and PI3K/Akt signaling pathway of human breast cancer MCF-7 cells. METHODS The breast cancer MCF-7 cells treated with different concentrations of ginsenoside CK had their cell proliferation,cell apoptosis,mRNA expressions of E-cadherin,N-cadherin and vimentin,protein expressions of p-PI3K and p-Akt detected by MTT,flow cytometry,real-time q PCR and Western blot,respectively. RESULTS Compared with the control group,groups treated with 10 μmol/L ginsenoside CK for 72 h,and 20μmol/L,40μmol/L,80 μmol/L ginsenoside CK for 24,48,72 h,respectively,shared significantly increased inhibition rates of cell proliferation( P <0. 05); groups treated with 20,40,80 μmol/L ginsenoside CK for 48 h shared obviously increased cell apoptosis rate and E-cadherin mRNA expression( P < 0. 05); groups treated with 20,40,80 μmol/L ginsenoside CK for48 h were found with markedly decreased N-cadherin,vimentin mRNA expressions,and p-PI3K,p-Akt protein expressions( P < 0. 05). CONCLUSION Ginsenoside CK' s inhibition on the proliferation and epithelial-mesenchymal transition of MCF-7 cells,and induction of cell apoptosis may be related to the inhibition of PI3K/Akt signaling pathway.
AIM To explore the effects of ginsenoside CK on the proliferation,apoptosis,epithelial-mesenchymal transition and PI3K/Akt signaling pathway of human breast cancer MCF-7 cells. METHODS The breast cancer MCF-7 cells treated with different concentrations of ginsenoside CK had their cell proliferation,cell apoptosis,mRNA expressions of E-cadherin,N-cadherin and vimentin,protein expressions of p-PI3K and p-Akt detected by MTT,flow cytometry,real-time q PCR and Western blot,respectively. RESULTS Compared with the control group,groups treated with 10 μmol/L ginsenoside CK for 72 h,and 20μmol/L,40μmol/L,80 μmol/L ginsenoside CK for 24,48,72 h,respectively,shared significantly increased inhibition rates of cell proliferation( P <0. 05); groups treated with 20,40,80 μmol/L ginsenoside CK for 48 h shared obviously increased cell apoptosis rate and E-cadherin mRNA expression( P < 0. 05); groups treated with 20,40,80 μmol/L ginsenoside CK for48 h were found with markedly decreased N-cadherin,vimentin mRNA expressions,and p-PI3K,p-Akt protein expressions( P < 0. 05). CONCLUSION Ginsenoside CK' s inhibition on the proliferation and epithelial-mesenchymal transition of MCF-7 cells,and induction of cell apoptosis may be related to the inhibition of PI3K/Akt signaling pathway.
引文
[1]何道同,王兵,陈珺明.人参皂苷药理作用研究进展[J].辽宁中医药大学学报,2012,14(7):118-121.
[2]Akao T,Kida H,Kanaoka M,et al.Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1from Panax ginseng[J].J Pharm Pharmacol,1998,50(10):1155-1160.
[3]张雷明,傅风华,王天,等.人参皂苷CK对四氯化碳致大鼠慢性肝损伤的影响[J].时珍国医国药,2006,17(1):38-39.
[4]刘伟,缪建春.人参皂苷CK的抗炎及神经保护作用研究[J].中国医药导报,2013,10(21):13-16,20.
[5]汪晶,杨蕾,金鑫,等.黄芪甲苷对人参皂苷CK肿瘤细胞摄取及抗肿瘤作用的影响[J].中草药,2016,47(13):2308-2312.
[6]荀平,孙莉.人参皂苷CK对大鼠心肌缺血再灌注损伤的保护作用及机制探讨[J].中国实验方剂学杂志,2016,22(16):155-158.
[7]邓晶,蒋永新.人参皂苷CK抗肿瘤活性研究进展[J].现代肿瘤医学,2009,17(11):2234-2236.
[8]Wenzel E S,Singh A T K.Cell-cycle checkpoints and aneuploidy on the path to cancer[J].In Vivo,2018,32(1):1-5.
[9]Mayer S A,Solimando D A,Waddell J A.Cancer chemotherapy update:bevacizumab,etoposide,and cisplatin regimen for refractory brain metastases[J].Hosp Pharm,2017,52(6):394-399.
[10]李馨刚.葛根素对乳腺癌细胞MCF-7增殖及凋亡的影响[J].中国老年学杂志,2015,35(15):4167-4169.
[11]卢晓燕,王琰,陈旻静,等.三七总苷抑制黑色素瘤A375细胞增殖的作用及机制研究[J].中药材,2017,40(5):1199-1202.
[12]Ando M,Yonemori K,Katsumata N,et al.PhaseⅠand pharmacokinetic study of nab-paclitaxel,nanoparticle albuminbound paclitaxel,administered weekly to Japanese patients with solid tumors and metastatic breast cancer[J].Cancer Chemother Pharmacol,2012,69(2):457-465.
[13]张晶,吕镇城,郑倩,等.金线莲抗肿瘤活性部位的体外筛选及对Lo Vo细胞凋亡的影响[J].中成药,2017,39(7):1507-1511.
[14]Li W,Liu Y,Zhang J W,et al.Anti-androgen-independent prostate cancer effects of ginsenoside metabolites in vitro:mechanism and possible structure-activity relationship investigation[J].Arch Pharm Res,2009,32(1):49-57.
[15]Cho S H,Chung K S,Choi J H,et al.Compound K,a metabolite of ginseng saponin,induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells[J].BMC Cancer,2009,9:449.
[16]Qin Y,Yang G,Li M,et al.Dihydroartemisinin inhibits EMT induced by platinum-based drugs via Akt-Snail pathway[J].Oncotarget,2017,8(61):103815-103827.
[17]Feng L M,Wang X F,Huang Q X.Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/m TOR pathway[J].J Biosci,2017,42(4):547-554.
[18]陈冬雪,陈亮.刺五加皂苷对人胃癌SGC-7901细胞增殖、凋亡、EMT及VEGF、b FGF表达的影响[J].中药材,2016,39(4):880-882.
[19]胡泽成.青龙衣多糖对结肠癌HCT-116细胞增殖、凋亡及PI3K/Akt信号通路的影响[J].中国实验方剂学杂志,2016,22(18):136-139.
[20]Ha G H,Park J S,Breuer E K.TACC3 promotes epithelialmesenchymal transition(EMT)through the activation of PI3K/Akt and ERK signaling pathways[J].Cancer Lett,2013,332(1):63-73.
[21]Yang J,Zeng Z,Peng Y,et al.IL-7 splicing variant IL-7δ5 induces EMT and metastasis of human breast cancer cell lines MCF-7 and BT-20 through activation of PI3K/Akt pathway[J].Histochem Cell Biol,2014,142(4):401-410.
[2]Akao T,Kida H,Kanaoka M,et al.Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1from Panax ginseng[J].J Pharm Pharmacol,1998,50(10):1155-1160.
[3]张雷明,傅风华,王天,等.人参皂苷CK对四氯化碳致大鼠慢性肝损伤的影响[J].时珍国医国药,2006,17(1):38-39.
[4]刘伟,缪建春.人参皂苷CK的抗炎及神经保护作用研究[J].中国医药导报,2013,10(21):13-16,20.
[5]汪晶,杨蕾,金鑫,等.黄芪甲苷对人参皂苷CK肿瘤细胞摄取及抗肿瘤作用的影响[J].中草药,2016,47(13):2308-2312.
[6]荀平,孙莉.人参皂苷CK对大鼠心肌缺血再灌注损伤的保护作用及机制探讨[J].中国实验方剂学杂志,2016,22(16):155-158.
[7]邓晶,蒋永新.人参皂苷CK抗肿瘤活性研究进展[J].现代肿瘤医学,2009,17(11):2234-2236.
[8]Wenzel E S,Singh A T K.Cell-cycle checkpoints and aneuploidy on the path to cancer[J].In Vivo,2018,32(1):1-5.
[9]Mayer S A,Solimando D A,Waddell J A.Cancer chemotherapy update:bevacizumab,etoposide,and cisplatin regimen for refractory brain metastases[J].Hosp Pharm,2017,52(6):394-399.
[10]李馨刚.葛根素对乳腺癌细胞MCF-7增殖及凋亡的影响[J].中国老年学杂志,2015,35(15):4167-4169.
[11]卢晓燕,王琰,陈旻静,等.三七总苷抑制黑色素瘤A375细胞增殖的作用及机制研究[J].中药材,2017,40(5):1199-1202.
[12]Ando M,Yonemori K,Katsumata N,et al.PhaseⅠand pharmacokinetic study of nab-paclitaxel,nanoparticle albuminbound paclitaxel,administered weekly to Japanese patients with solid tumors and metastatic breast cancer[J].Cancer Chemother Pharmacol,2012,69(2):457-465.
[13]张晶,吕镇城,郑倩,等.金线莲抗肿瘤活性部位的体外筛选及对Lo Vo细胞凋亡的影响[J].中成药,2017,39(7):1507-1511.
[14]Li W,Liu Y,Zhang J W,et al.Anti-androgen-independent prostate cancer effects of ginsenoside metabolites in vitro:mechanism and possible structure-activity relationship investigation[J].Arch Pharm Res,2009,32(1):49-57.
[15]Cho S H,Chung K S,Choi J H,et al.Compound K,a metabolite of ginseng saponin,induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells[J].BMC Cancer,2009,9:449.
[16]Qin Y,Yang G,Li M,et al.Dihydroartemisinin inhibits EMT induced by platinum-based drugs via Akt-Snail pathway[J].Oncotarget,2017,8(61):103815-103827.
[17]Feng L M,Wang X F,Huang Q X.Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/m TOR pathway[J].J Biosci,2017,42(4):547-554.
[18]陈冬雪,陈亮.刺五加皂苷对人胃癌SGC-7901细胞增殖、凋亡、EMT及VEGF、b FGF表达的影响[J].中药材,2016,39(4):880-882.
[19]胡泽成.青龙衣多糖对结肠癌HCT-116细胞增殖、凋亡及PI3K/Akt信号通路的影响[J].中国实验方剂学杂志,2016,22(18):136-139.
[20]Ha G H,Park J S,Breuer E K.TACC3 promotes epithelialmesenchymal transition(EMT)through the activation of PI3K/Akt and ERK signaling pathways[J].Cancer Lett,2013,332(1):63-73.
[21]Yang J,Zeng Z,Peng Y,et al.IL-7 splicing variant IL-7δ5 induces EMT and metastasis of human breast cancer cell lines MCF-7 and BT-20 through activation of PI3K/Akt pathway[J].Histochem Cell Biol,2014,142(4):401-410.