CN: 32-1845/R
ISSN: 2095-6975
引用本文:
0
ZHAO Ya-Zheng, ZHANG Yuan-Yuan, HAN Han, FAN Rui-Ping, HU Yang, ZHONG Liang, KOU Jun-Ping, YU Bo-Yang. Advances in the antitumor activities and mechanisms of action of steroidal saponins[J]. 中国天然药物英文, 2018, 16(10): 732-748

Advances in the antitumor activities and mechanisms of action of steroidal saponins

ZHAO Ya-Zheng, ZHANG Yuan-Yuan, HAN Han, FAN Rui-Ping, HU Yang, ZHONG Liang, KOU Jun-Ping, YU Bo-Yang
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 211198, China
摘要:
The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.
关键词:    Steroidal saponins    Tumor    Mechanism   
收稿日期: 2018-01-20
KOU Jun-Ping,E-mail:junpingkou@cpu.edu.cn;YU Bo-Yang,E-mail:boyangyu59@163.com
相关功能
PDF(2127 KB) Free
打印本文
把本文推荐给朋友
作者相关文章
ZHAO Ya-Zheng 在本刊中的所有文章
ZHANG Yuan-Yuan 在本刊中的所有文章
HAN Han 在本刊中的所有文章
FAN Rui-Ping 在本刊中的所有文章
HU Yang 在本刊中的所有文章
ZHONG Liang 在本刊中的所有文章
KOU Jun-Ping 在本刊中的所有文章
YU Bo-Yang 在本刊中的所有文章
参考文献:
[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017[J]. CA Cancer J Clin, 2015, 60(5):277-300.
[2] Lutgendorf S, Anderson B N, Buller R, et al. Quality of life and mood in women receiving extensive chemotherapy for gynecologic cancer[J]. Cancer, 2015, 89(6):1402-1411.
[3] Kharb Manju, Jat RK, Gupta Anju. A review on medicinal plants used as a source of anticancer agents[J]. Int J Drug Res Tech, 2012, 2(2):177-183.
[4] Roy A, Attre T, Bharadvaja N. Anticancer Agent from Medicinal Plants:A Review[M]. New aspects in medicinal plants and pharmacognosy, 2017.
[5] Butler MS. Natural products to drugs:natural prod-uct-derived compounds in clinical trials[J]. Nat Prod Rep, 2008, 25(3):475-516.
[6] Ma S, Kou J, Yu B. Safety evaluation of steroidal saponin DT-13 isolated from the tuber of Liriope muscari (Decne.) Baily[J]. Food Chem Toxicol, 2011, 49(9):2243-2251.
[7] Li YW, Qi J, Zhang YY, et al. Novel cytotoxic steroidal glycosides from the roots of Liriope muscari[J]. Chin J Nat Med, 2015, 13(6):461-466.
[8] Zhu GL, Hao Q, Li RT, et al. Steroidal saponins from the roots of Asparagus cochinchinensis[J]. Chin J Nat Med, 2014, 12(3):213-217.
[9] Zheng L, Zhou Y, Zhang JY, et al. Two new steroidal saponins from the rhizomes of Dioscorea zingiberensis[J]. Chin J Nat Med, 2014, 12(2):142-147.
[10] Hao DC, Gu XJ, Xiao PG, et al. Phytochemical and biological research of Fritillaria medicine resources[J]. Chin J Nat Med, 2013, 11(4):330-344.
[11] Liu M, Zhao X, Xiao L, et al. Cytotoxicity of the compounds isolated from Pulsatilla chinensis saponins and apoptosis induced by 23-hydroxybetulinic acid[J]. Pharm Biol, 2015, 53(1):1-9.
[12] Kirmizibekmez H, Masullo M, Festa M, et al. Steroidal glycosides with antiproliferative activities from Digitalis trojana[J]. Phytother Res, 2014, 28(4):534-538.
[13] Mohammad RY, Somayyeh G, Gholamreza H, et al. Diosgenin inhibits hTERT gene expression in the A549 lung cancer cell line[J]. Asian Pac J Cancer Prev, 2013, 14(11):6945-6948.
[14] Bian D, Li Z, Ma H, et al. Effects of diosgenin on cell proliferation induced by IGF-1 in primary human thy-rocytes[J]. Arch Pharm Res, 2011, 34(6):997-1005.
[15] Cai H, Wang Z, Zhang HQ, et al. Diosgenin relieves goiter via the inhibition of thyrocyte proliferation in a mouse model of Graves' disease[J]. Acta Pharmacol Sin, 2014, 35(1):65-73.
[16] Li F, Fernandez PP, Rajendran P, et al. Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells[J]. Cancer Lett, 2010, 292(2):197-207.
[17] Wu X, Wang L, Wang H, et al. Steroidal saponins from Paris polyphylla var. yunnanensis[J]. Phytochemistry, 2012, 81:133-143.
[18] Li W, Song R, Fang X, et al. SBF-1, a synthetic steroidal glycoside, inhibits melanoma growth and metastasis through blocking interaction between PDK1 and AKT3[J]. Biochem Pharmacol, 2012, 84(2):172-181.
[19] Thao NP, Luyen BTT, Kim EJ. Asterosaponins from the starfish Astropecten monacanthus suppress growth and induce apoptosis in HL-60, PC-3, and SNU-C5 human cancer cell lines[J]. Biol Pharm Bull, 2014, 37(2):315-321.
[20] Zhao Y, Zhu C, Li X, et al. Asterosaponin 1 induces endoplasmic reticulum stress-associated apoptosis in A549 human lung cancer cells[J]. Oncol Rep, 2011, 26(4):919-924.
[21] Chen GL, Gao WS, Hou GL, et al. Effect of Paris saponin on antitumor and immune function in U14 tu-mor-bearing mice[J]. Afr J Tradit Complement Altern Med, 2013, 10(3):503-507.
[22] Yan S, Tian S, Kang Q, et al. Rhizoma paridis saponins suppresses tumor growth in a rat model of N-nitrosomethylbenzylamine-induced esophageal cancer by inhibiting cyclooxygenases-2 pathway[J]. PLoS One, 2015, 10(7):e0131560.
[23] Liu J, Man S, Li J, et al. Inhibition of diethylnitrosamine-induced liver cancer in rats by Rhizoma paridis saponin[J]. Environ Toxicol Pharmacol, 2016, 46:103-109.
[24] Liu J, Liu Z, Man S, et al. Inhibition of urethane-induced lung carcinogenesis in mice by a Rhizoma paridis saponin involved EGFR/PI3K/Akt pathway[J]. RSC Adv, 2016, 6(95):92330-92334.
[25] Auyeung KK, Law PC, Ko JK. Combined therapeutic effects of vinblastine and Astragalus saponins in human colon cancer cells and tumor xenograft via inhibition of tumor growth and proangiogenic factors[J]. Nutr Cancer, 2014, 66(4):662-674.
[26] Liu Z, Zheng Q, Chen W, et al. Chemosensitizing effect of Paris Saponin I on Camptothecin and 10-hydroxycamptothecin in lung cancer cells via p38 MAPK, ERK, and Akt signaling pathways[J]. Eur J Med Chem, 2017, 125:760-769.
[27] Zhu X, Jiang H, Li J, et al. Anticancer effects of paris saponins by apoptosis and PI3K/AKT pathway in gefitinib-resistant non-small cell lung cancer[J]. Med Sci Monitor, 2016, 22:1435-1441.
[28] Kang XH, Xu ZY, Gong YB, et al. Bufalin reverses HGF-induced resistance to EGFR-TKIs in EGFR mutant lung cancer cells via blockage of Met/PI3k/Akt pathway and induction of apoptosis[J]. Evid Based Complement Alternat Med, 2013, 2013(10):243859.
[29] Gu L, Feng J, Xu H, et al. Polyphyllin I inhibits proliferation and metastasis of ovarian cancer cell line HO-8910PM in vitro[J]. J Tradit Chin Med, 2013, 33(3):325-333.
[30] Wang H, Zhai Z, Li N, et al. Steroidal saponin of Trillium tschonoskii. Reverses multidrug resistance of hepatocellular carcinoma[J]. Phytomedicine, 2013, 20(11):985-991.
[31] Li N, Zhang L, Zeng KW, et al. Cytotoxic steroidal saponins from Ophiopogon japonicus[J]. Steroids, 2013, 78(1):1-7.
[32] Waheed A, Barker J, Barton SJ, et al. A novel steroidal saponin glycoside from Fagonia indica induces cell-selective apoptosis or necrosis in cancer cells[J]. Eur J Pharm Sci, 2012, 47(2):464-473.
[33] Tong QY, He Y, Zhao QB, et al. Cytotoxicity and apop-tosis-inducing effect of steroidal saponins from Dioscorea zingiberensis Wright against cancer cells[J]. Steroids, 2012, 77(12):1219-1227.
[34] Liang F, He JW, Zhu GH, et al. New steroidal saponins with cytotoxic activities from Smilax trinervula[J]. Phytochemistry Lett, 2016, 16:294-298.
[35] Haiming Z, Junli Z, Hao D. Clinical value of Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract combined chemotherapy in the treatment of advanced non-small cell lung cancer:a Meta-analysis[J]. J Tradit Chin Med, 2016, 36(3):261-270.
[36] Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy[J]. Cancer, 2015, 73(8):2013-2026.
[37] Hassan M, Watari H, AbuAlmaaty A, et al. Apoptosis and molecular targeting therapy in cancer[J]. Biomed Res Int, 2014, 2014(2):150845.
[38] Mu S, Tian X, Ruan Y, et al. Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two cas-pase-dependent pathways[J]. Biochem Bioph Res Co, 2012, 418(2):347-352.
[39] Kim DS, Jeon BK, Lee YE, et al. Diosgenin induces apoptosis in HepG2 cells through generation of reactive oxygen species and mitochondrial pathway[J]. Evid Based Complement Alternat Med, 2012, 2012(2):981675.
[40] Jan TR, Wey SP, Kuan CC, et al. Diosgenin, a steroidal sapogenin, enhances antigen-specific IgG2a and in-terferon-gamma expression in ovalbumin-sensitized BALB/c mice[J]. Planta Med, 2007, 73(5):421-426.
[41] Uemura T, Goto T, Kang MS, et al. Diosgenin, the main aglycon of fenugreek, inhibits LXRalpha activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice[J]. J Nutr, 2011, 141(1):17-23.
[42] Jung DH, Park HJ, Byun HE, et al. Diosgenin inhibits macrophage-derived inflammatory mediators through downregulation of CK2, JNK, NF-kappaB and AP-1 activation[J]. Int Immunopharmacol, 2010, 10(9):1047-1054.
[43] Lepage C, Liagre B, Cook-Moreau J, et al. Cyclooxygenase-2 and 5-lipoxygenase pathways in diosgenin-induced apoptosis in HT-29 and HCT-116 colon cancer cells[J]. Int J Oncol, 2010, 36(5):1183-1191.
[44] Lepage C, Leger DY, Bertrand J, et al. Diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis in colon cancer cells[J]. Cancer Lett, 2011, 301(2):193-202.
[45] Wang X, Sun C, He S, et al. Apoptotic effects of diosgeninlactoside on oral squamous carcinoma cells in vitro and in vivo[J]. Biol Pharm Bull, 2014, 37(9):1450-1459.
[46] Chun J, Han L, Xu MY, et al. The induction of apoptosis by a newly synthesized diosgenyl saponin through the suppression of estrogen receptor-alpha in MCF-7 human breast cancer cells[J]. Arch Pharm Res, 2014, 37(11):1477-1486.
[47] Dong Y, Yin S, Li J, et al. Bufadienolide compounds sensitize human breast cancer cells to TRAIL-induced apoptosis via inhibition of STAT3/Mcl-1 pathway[J]. Apoptosis, 2011, 16(4):394-403.
[48] Zhang DM, Liu JS, Deng LJ, et al. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway[J]. Carcinogenesis, 2013, 34(6):1331-1342.
[49] Liu W, Ning R, Chen RN, et al. Aspafilioside B induces G2/M cell cycle arrest and apoptosis by up-regulating H-Ras and N-Ras via ERK and p38 MAPK signaling pathways in human hepatoma HepG2 cells[J]. Mol Carcinogen, 2016, 55(5):440-457.
[50] Yin PH, Liu X, Qiu YY, et al. Anti-tumor activity and apoptosis-regulation mechanisms of bufalin in various cancers:new hope for cancer patients[J]. Asian Pac J Cancer Prev, 2012, 13(11):5339-5343.
[51] Zhu Z, Li E, Liu Y, et al. Inhibition of Jak-STAT3 pathway enhances bufalin-induced apoptosis in colon cancer SW620 cells[J]. World J Surg Oncol, 2012, 10(1):228.
[52] Waiwut P, Inujima A, Inoue H, et al. Bufotalin sensitizes death receptor-induced apoptosis via Bid-and STAT1-dependent pathways[J]. Int J Oncol, 2012, 40(1):203-208.
[53] Zhao L, Shan B, Du Y, et al. Periplocin from Cortex periplocae inhibits cell growth and down-regulates survivin and c-myc expression in colon cancer in vitro and in vivo via beta-catenin/TCF signaling[J]. Oncol Rep, 2010, 24(2):375-383.
[54] Lu ZJ, Zhou Y, Song Q, et al. Periplocin inhibits growth of lung cancer in vitro and in vivo by blocking AKT/ERK signaling pathways[J]. Cell Physiol Biochem, 2010, 26(4-5):609-618.
[55] Lv L, Zheng L, Dong D, et al. Dioscin, a natural steroid saponin, induces apoptosis and DNA damage through reactive oxygen species:a potential new drug for treatment of glioblastoma multiforme[J]. Food Chem Toxicol, 2013, 59(3):657-669.
[56] Kim EA, Jang JH, Lee YH, et al. Dioscin induces caspase-independent apoptosis through activation of apop-tosis-inducing factor in breast cancer cells[J]. Apoptosis, 2014, 19(7):1165-1175.
[57] Wang Y, He QY, Chiu JF. Dioscin induced activation of p38 MAPK and JNK via mitochondrial pathway in HL-60 cell line[J]. Eur J Pharmacol, 2014, 735(14):52-58.
[58] Li Y, Liu C, Xiao D, et al. Trillium tschonoskii steroidal saponins suppress the growth of colorectal Cancer cells in vitro and in vivo[J]. J Ethnopharmacol, 2015, 168:136-145.
[59] Sun H, Lv C, Yang L, et al. Solanine induces mitochon-dria-mediated apoptosis in human pancreatic cancer cells[J]. Biomed Res Int, 2014, 2014(3):805926.
[60] Jin J, Jin X, Qian C, et al. Signaling network of OSW1induced apoptosis and necroptosis in hepatocellular carcinoma[J]. Mol Med Rep, 2013, 7(5):1646-1650.
[61] Garcia-Prieto C, Riaz Ahmed KB, Chen Z, et al. Effective killing of leukemia cells by the natural product OSW-1 through disruption of cellular calcium homeostasis[J]. J Biol Chem, 2013, 288(5):3240-3250.
[62] Wang G, Huang W, He H, et al. Growth inhibition and apoptosis-inducing effect on human cancer cells by RCE-4, a spirostanol saponin derivative from natural medicines[J]. Int J Mol Med, 2013, 31(1):219-224.
[63] Bai C, Yang X, Zou K, et al. Anti-proliferative effect of RCE-4 from Reineckia carnea on human cervical cancer HeLa cells by inhibiting the PI3K/Akt/mTOR signaling pathway and NF-kappaB activation[J]. Naunyn Schmiedebergs Arch Pharmacol, 2016, 389(6):573-584.
[64] Jaramillo S, Muriana FJG, Guillen R, et al. Saponins from edible spears of wild asparagus inhibit AKT, p70S6K, and ERK signalling, and induce apoptosis through G0/G1 cell cycle arrest in human colon cancer HCT-116 cells[J]. J Funct Foods, 2016, 26:1-10.
[65] Li Y, Gu JF, Zou X, et al. The anti-lung cancer activities of steroidal saponins of P. polyphylla Smith var. chinensis (Franch.) Hara through enhanced immunostimulation in experimental Lewis tumor-bearing C57BL/6 mice and in-duction of apoptosis in the A549 cell line[J]. Molecules, 2013, 18(10):12916-12936.
[66] Teng WJ, Chen P, Zhu FY, et al. Effect of Rhizoma paridis total saponins on apoptosis of colorectal cancer cells and imbalance of the JAK/STAT3 molecular pathway induced by IL-6 suppression[J]. Genet Mol Res, 2015, 14(2):5793-5803.
[67] Long FY, Chen YS, Zhang L, et al. Pennogenyl saponins induce cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells[J]. J Ethnopharmacol, 2015, 162:112-120.
[68] Zhao P, Jiang H, Su D, et al. Inhibition of cell proliferation by mild hyperthermia at 43 C with Paris Saponin I in the lung adenocarcinoma cell line PC-9[J]. Mol Med Rep, 2015, 11(1):327-332.
[69] GuangLie C, WeiShi G, GaiLing H, et al. Effect of Paris saponin on antitumor and immune function in U14 tu-mor-bearing mice[J]. Afr J Tradit Complement Altern Med, 2013, 10(3):503-507.
[70] Zhang W, Zhang D, Ma X, et al. Paris saponin VⅡ suppressed the growth of human cervical cancer Hela cells[J]. Eur J Med Res, 2014, 19:41-48.
[71] Li Y, Sun Y, Fan L, et al. Paris saponin VⅡ inhibits growth of colorectal cancer cells through Ras signaling pathway[J]. Biochem Pharmacol, 2014, 88(2):150-157.
[72] Li Y, Fan L, Sun Y, et al. Paris saponin VⅡ from trillium tschonoskii reverses multidrug resistance of adriamycin-resistant MCF-7/ADR cells via P-glycoprotein inhibition and apoptosis augmentation[J]. J Ethnopharmacol, 2014, 154(3):728-734.
[73] Zeng KW, Li N, Dong X, et al. Sprengerinin C exerts an-ti-tumorigenic effects in hepatocellular carcinoma via inhibition of proliferation and angiogenesis and induction of apoptosis[J]. Eur J Pharmacol, 2013, 714(1-3):261-273.
[74] Wang N, Feng Y, Zhu M, et al. A novel mechanism of XIAP degradation induced by timosaponin AⅢ in hepatocellular carcinoma[J]. Biochim Biophys Acta, 2013, 1833(12):2890-2899.
[75] Wang Y, Tang Q, Jiang S, et al. Anti-colorectal cancer activity of macrostemonoside A mediated by reactive oxygen species[J]. Biochem Bioph Res Co, 2013, 441(4):825-830.
[76] Zhang W, Zhang Q, Jiang Y, et al. Effects of ophiopogonin B on the proliferation and apoptosis of SGC7901 human gastric cancer cells[J]. Mol Med Rep, 2016, 13(6):4981-4986.
[77] Fulda S, Kogel D. Cell death by autophagy:emerging molecular mechanisms and implications for cancer therapy[J]. Oncogene, 2015, 34(40):5105-5113.
[78] He H, Sun YP, Zheng L, et al. Steroidal saponins from Paris polyphylla induce apoptotic cell death and autophagy in A549 human lung cancer cells[J]. Asian Pac J Cancer Prev, 2015, 16(3):1169-1173.
[79] Chen M, Du Y, Qui M, et al. Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway[J]. Oncol Rep, 2013, 29(2):430-436.
[80] Chen M, Guo Y, Zhao R, et al. Ophiopogonin B induces apoptosis, mitotic catastrophe and autophagy in A549 cells[J]. Int J Oncol, 2016, 49(1):316-324.
[81] Kim WK, Pyee Y, Chung HJ, et al. Antitumor activity of Spicatoside A by modulation of autophagy and apoptosis in human colorectal cancer cells[J]. J Nat Prod, 2016, 79(4):1097-1104.
[82] Yu L, Mu Y, Sa N, et al. Tumor necrosis factor alpha induces epithelial-mesenchymal transition and promotes metastasis via NF-kappaB signaling pathway-mediated TWIST expression in hypopharyngeal cancer[J]. Oncol Rep, 2014, 31(1):321-327.
[83] Gao Y, Li G, Sun L, et al. ACTN4 and the pathways associated with cell motility and adhesion contribute to the process of lung cancer metastasis to the brain[J]. BMC Cancer, 2015, 15(1):277-285.
[84] Zins K, Lucas T, Reichl P, et al. A Rac1/Cdc42 GTPase-specific small molecule inhibitor suppresses growth of primary human prostate cancer xenografts and prolongs survival in mice[J]. PLoS One, 2013, 8(9):e74924.
[85] He Z, Chen H, Li G, et al. Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity[J]. Phytomedicine, 2014, 21(6):871-876.
[86] Chen PS, Shih YW, Huang HC, et al. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression[J]. PLoS One, 2011, 6(5):e20164.
[87] Qiu P, Man S, Yang H, et al. Metabolic regulatory network alterations reveal different therapeutic effects of cisplatin and Rhizoma paridis saponins in Lewis pulmonary adenoma mice[J]. RSC Adv, 2016, 6(116):115029-115038.
[88] Cheng G, Gao F, Sun X, et al. Paris saponin VⅡ suppresses osteosarcoma cell migration and invasion by inhibiting MMP2/9 production via the p38 MAPK signaling pathway[J]. Mol Med Rep, 2016, 14(4):3199-3205.
[89] Zhang Y, Han Y, Zhai K, et al. Ophiopogonin-D suppresses MDA-MB-435 cell adhesion and invasion by inhibiting matrix metalloproteinase-9[J]. Mol Med Rep, 2015, 12(1):1493-1498.
[90] Zhao R, Sun L, Lin S, et al. The saponin monomer of dwarf lilyturf tuber, DT-13, inhibits angiogenesis under hypoxia and normoxia via multi-targeting activity[J]. Oncol Rep, 2013, 29(4):1379-1386.
[91] Zhang Y, Liu J, Kou J, et al. DT-13 suppresses MDA-MB-435 cell adhesion and invasion by inhibiting MMP-2/9 via the p38 MAPK pathway[J]. Mol Med Rep, 2012, 6(5):1121-1125.
[92] Zhao RP, Lin SS, Yuan ST, et al. DT-13, a saponin of dwarf lilyturf tuber, exhibits anti-cancer activity by down-regulating C-C chemokine receptor type 5 and vascular endothelial growth factor in MDA-MB-435 cells[J]. Chin J Nat Med, 2014, 12(1):24-29.
[93] Zhang Y, Liu J, Kou J, et al. DT-13, a steroidal saponin from Liriope muscari L. H. Bailey, suppresses A549 cells adhesion and invasion by inhibiting MMP-2/9[J]. Chin J Nat Med, 2012, 10(6):436-440.
[94] Lin SS, Fan W, Sun L, et al. The saponin DT-13 inhibits gastric cancer cell migration through down-regulation of CCR5-CCL5 axis[J]. Chin J Nat Med, 2014, 12(11):833-840.
[95] Qiu DZ, Zhang ZJ, Wu WZ, et al. Bufalin, a component in Chansu, inhibits proliferation and invasion of hepatocellular carcinoma cells[J]. BMC Complement Altern Med, 2013, 13(1):185.
[96] Zhang T, Li J, Dong Y, et al. Cucurbitacin E inhibits breast tumor metastasis by suppressing cell migration and invasion[J]. Breast Cancer Res Treat, 2012, 135(2):445-458.
[97] Jung O, Lee J, Lee YJ, et al. Timosaponin AⅢ inhibits migration and invasion of A549 human non-small-cell lung cancer cells via attenuations of MMP-2 and MMP-9 by inhibitions of ERK1/2, Src/FAK and beta-catenin signaling pathways[J]. Bioorg Med Chem Lett, 2016, 26(16):3963-3967.
[98] Roudsari LC, West JL. Studying the influence of angiogenesis in in vitro, cancer model systems[J]. Adv Drug Deliver Rev, 2016, 97:250-259.
[99] Das S, Dey KK, Dey G, et al. Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma[J]. PLoS One, 2012, 7(10):e46641.
[100] Xiao X, Yang M, Xiao J, et al. Paris Saponin Ⅱ suppresses the growth of human ovarian cancer xenografts via modulating VEGF-mediated angiogenesis and tumor cell migration[J]. Cancer Chemother Pharmacol, 2014, 73(4):807-818.
[101] Wei S, Fukuhara H, Chen G, et al. Terrestrosin D, a steroidal saponin from Tribulus terrestris L. inhibits growth and angiogenesis of human prostate cancer in vitro and in vivo[J]. Pathobiology, 2014, 81(3):123-132.
[102] Piao XM, Gao F, Zhu JX, et al. Cucurbitacin B inhibits tumor angiogenesis by triggering the mitochondrial signaling pathway in endothelial cells[J]. Int J Mol Med, 2018, 42(2):1018-1025.
[103] Mao ZJ, Tang QJ, Zhang CA, et al. Anti-proliferation and anti-invasion effects of diosgenin on gastric cancer BGC-823 cells with HIF-1alpha shRNAs[J]. Int J Mol Sci, 2012, 13(5):6521-6533.
[104] Jin JC, Jin XL, Zhang X, et al. Effect of OSW-1 on microRNA expression profiles of hepatoma cells and functions of novel microRNAs[J]. Mol Med Rep, 2013, 7(6):1831-1837.
[105] Chang HY, Kao MC, Way TD, et al. Diosgenin suppresses hepatocyte growth factor (HGF)-induced epithe-lial-mesenchymal transition by down-regulation of Mdm2 and vimentin[J]. J Agric Food Chem, 2011, 59(10):5357-5363.
[106] Wang WC, Liu SF, Chang WT, et al. The effects of diosgenin in the regulation of renal proximal tubular fibrosis[J]. Exp Cell Res, 2014, 323(2):255-262.