Polyphyllin II inhibits human bladder cancer migration and invasion by regulating EMT‑associated factors and MMPs

Niu,Weipin; Xu,Li; Li,Jingwei; Zhai,Yi; Sun,Zhonghua; Shi,Wei; Jiang,Yuehua; Ma,Chenchen; Lin,Haiqing; Guo,Yanxia; Liu,Zhiyong

doi:10.3892/ol.2020.11839

Polyphyllin II inhibits human bladder cancer migration and invasion by regulating EMT‑associated factors and MMPs

Authors:
- Weipin Niu
- Li Xu
- Jingwei Li
- Yi Zhai
- Zhonghua Sun
- Wei Shi
- Yuehua Jiang
- Chenchen Ma
- Haiqing Lin
- Yanxia Guo
- Zhiyong Liu
View Affiliations

Affiliations: Central Laboratory, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China, Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Breast Surgery, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China, Medical Department, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China, Department of Gynecology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China, Engineering Laboratory of Shandong Province for Structure and Functional Reconstruction of Urinary Organs, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: July 9, 2020 https://doi.org/10.3892/ol.2020.11839
Pages: 2928-2936
Copyright: © Niu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The epithelial‑mesenchymal transition (EMT) serves vital roles in the angiogenesis, cell invasion and metastasis of various malignant tumors, including bladder cancer. Traditional Chinese medicinal herbs have been demonstrated to exhibit anticancer properties. The present study aimed to screen the sensitivity of bladder cancer to natural compounds by using six classic anti‑inflammatory and detoxifying herbs, including the ethanol extract of Paris polyphylla (PPE), Scutellaria barbata, Pulsatillae decoction, Dahuang Huanglian Xiexin decoction, Bazhengsan and Hedyotis diffusa combined with S. barbata, were used to treat bladder cancer cells in vitro. Bladder cancer was more sensitive to PPE compared with the other tested herbs, and PPE significantly suppressed bladder cancer cell migration and invasion. Thus, the present study focused on PPE. Bladder cancer cells were treated with monomer components of PPE, including polyphyllin (PP) I, PPII, PPVI and PPVII. The results demonstrated that PPII treatment significantly inhibited cancer cell migration and invasion, increased the expression level of E‑cadherin and decreased the levels of N‑cadherin, snail family transcriptional repressor 2, twist family bHLH transcription factor 1, matrix metallopeptidase (MMP) 2 and MMP9 compared with those in the control group (untreated cells). These results suggested that PPII treatment may suppress bladder cancer cell migration and invasion by regulating the expression of EMT‑associated genes and MMPs. Therefore, PPE and PPII may have antimetastatic effects and PPII may serve as a potential therapeutic option for inhibiting bladder cancer metastasis.

View Figures

View References

1	Richters A, Aben KKH and Kiemeney LALM: The global burden of urinary bladder cancer: An update. World J Urol. Nov 1–2019.(Epub ahead of print). PubMed/NCBI
2	Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A and Bray F: Bladder cancer incidence and mortality: A global overview and recent trends. Eur Urol. 71:96–108. 2017. View Article : Google Scholar : PubMed/NCBI
3	Sharma S, Ksheersagar P and Sharma P: Diagnosis and treatment of bladder cancer. Am Fam Physician. 80:717–723. 2009.PubMed/NCBI
4	Allory Y, Beukers W, Sagrera A, Flández M, Marqués M, Márquez M, van der Keur KA, Dyrskjot L, Lurkin I, Vermeij M, et al: Telomerase reverse transcriptase promoter mutations in bladder cancer: High frequency across stages, detection in urine, and lack of association with outcome. Eur Urol. 65:360–366. 2014. View Article : Google Scholar : PubMed/NCBI
5	Kim WJ, Kim EJ, Kim SK, Kim YJ, Ha YS, Jeong P, Kim MJ, Yun SJ, Lee KM, Moon SK, et al: Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer. Mol Cancer. 9:32010. View Article : Google Scholar : PubMed/NCBI
6	Milowsky MI, Rumble RB, Booth CM, Gilligan T, Eapen LJ, Hauke RJ, Boumansour P and Lee CT: Guideline on Muscle-Invasive and Metastatic Bladder Cancer (European Association of Urology Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement. J Clin Oncol. 34:1945–1952. 2016. View Article : Google Scholar : PubMed/NCBI
7	Quirk JT and Kupinski JM: Chronic infection, inflammation, and epithelial ovarian cancer. Med Hypotheses. 57:426–428. 2001. View Article : Google Scholar : PubMed/NCBI
8	Balkwill F and Mantovani A: Inflammation and cancer: Back to Virchow? Lancet. 357:539–545. 2001. View Article : Google Scholar : PubMed/NCBI
9	Zhang Y, Liang Y and He C: Anticancer activities and mechanisms of heat-clearing and detoxicating traditional Chinese herbal medicine. Chin Med. 12:202017. View Article : Google Scholar : PubMed/NCBI
10	Man S, Gao W, Wei C and Liu C: Anticancer drugs from traditional toxic Chinese medicines. Phytother Res. 26:1449–1465. 2012.PubMed/NCBI
11	Lee MS, Yuet-Wa JC, Kong SK, Yu B, Eng-Choon VO, Nai-Ching HW, Chung-Wai TM and Fung KP: Effects of polyphyllin D, a steroidal saponin in Paris polyphylla, in growth inhibition of human breast cancer cells and in xenograft. Cancer Biol Ther. 4:1248–1254. 2005. View Article : Google Scholar : PubMed/NCBI
12	He H, Zheng L, Sun YP, Zhang GW and Yue ZG: Steroidal saponins from Paris polyphylla suppress adhesion, migration and invasion of human lung cancer A549 cells via down-regulating MMP-2 and MMP-9. Asian Pac J Cancer Prev. 15:10911–10916. 2014. View Article : Google Scholar : PubMed/NCBI
13	Xiao X, Zou J, Bui-Nguyen TM, Bai P, Gao L, Liu J, Liu S, Xiao J, Chen X, Zhang X, et al: Paris saponin II of Rhizoma Paridis - a novel inducer of apoptosis in human ovarian cancer cells. Biosci Trends. 6:201–211. 2012. View Article : Google Scholar : PubMed/NCBI
14	Commission CP: Pharmacopoeia of The People's Republic of China. 1:(1st). People's Medical Publishing House. (Beijing). 2015.
15	Huber MA, Kraut N and Beug H: Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 17:548–558. 2005. View Article : Google Scholar : PubMed/NCBI
16	Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI
17	Xiao T, Zhong W, Zhao J, Qian B, Liu H, Chen S, Qiao K, Lei Y, Zong S, Wang H, et al: Polyphyllin I suppresses the formation of vasculogenic mimicry via Twist1/VE-cadherin pathway. Cell Death Dis. 9:9062018. View Article : Google Scholar : PubMed/NCBI
18	Zhang Y, Huang P, Liu X, Xiang Y, Zhang T, Wu Y, Xu J, Sun Z, Zhen W, Zhang L, et al: Polyphyllin I inhibits growth and invasion of cisplatin-resistant gastric cancer cells by partially inhibiting CIP2A/PP2A/Akt signaling axis. J Pharmacol Sci. 137:305–312. 2018. View Article : Google Scholar : PubMed/NCBI
19	Hu H, Meng Q, Lei T and Zhang M: Nucleophosmin1 associated with drug resistance and recurrence of bladder cancer. Clin Exp Med. 15:361–369. 2015. View Article : Google Scholar : PubMed/NCBI
20	Fankhauser CD and Mostafid H: Prevention of bladder cancer incidence and recurrence: Nutrition and lifestyle. Curr Opin Urol. 28:88–92. 2018. View Article : Google Scholar : PubMed/NCBI
21	Hsiao WL and Liu L: The role of traditional Chinese herbal medicines in cancer therapy - from TCM theory to mechanistic insights. Planta Med. 76:1118–1131. 2010. View Article : Google Scholar : PubMed/NCBI
22	Chow SE, Chang YL, Chuang SF and Wang JS: Wogonin induced apoptosis in human nasopharyngeal carcinoma cells by targeting GSK-3β and ΔNp63. Cancer Chemother Pharmacol. 68:835–845. 2011. View Article : Google Scholar : PubMed/NCBI
23	Zhang Z, Lv J, Lei X, Li S, Zhang Y, Meng L, Xue R and Li Z: Baicalein reduces the invasion of glioma cells via reducing the activity of p38 signaling pathway. PLoS One. 9:e903182014. View Article : Google Scholar : PubMed/NCBI
24	Weifeng T, Feng S, Xiangji L, Changqing S, Zhiquan Q, Huazhong Z, Peining Y, Yong Y, Mengchao W, Xiaoqing J, et al: Artemisinin inhibits in vitro and in vivo invasion and metastasis of human hepatocellular carcinoma cells. Phytomedicine. 18:158–162. 2011. View Article : Google Scholar : PubMed/NCBI
25	Valastyan S and Weinberg RA: Tumor metastasis: Molecular insights and evolving paradigms. Cell. 147:275–292. 2011. View Article : Google Scholar : PubMed/NCBI
26	Fidler IJ and Kripke ML: The challenge of targeting metastasis. Cancer Metastasis Rev. 34:635–641. 2015. View Article : Google Scholar : PubMed/NCBI
27	De Craene B and Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 13:97–110. 2013. View Article : Google Scholar : PubMed/NCBI
28	Radisky DC: Epithelial-mesenchymal transition. J Cell Sci. 118:4325–4326. 2005. View Article : Google Scholar : PubMed/NCBI
29	Kudo-Saito C, Shirako H, Takeuchi T and Kawakami Y: Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell. 15:195–206. 2009. View Article : Google Scholar : PubMed/NCBI
30	Casas E, Kim J, Bendesky A, Ohno-Machado L, Wolfe CJ and Yang J: Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res. 71:245–254. 2011. View Article : Google Scholar : PubMed/NCBI
31	Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F and Liu Y: TGF beta induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12. Clin Cancer Res. 20:1531–1541. 2014. View Article : Google Scholar : PubMed/NCBI
32	Deryugina EI and Quigley JP: Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 25:9–34. 2006. View Article : Google Scholar : PubMed/NCBI
33	Halbersztadt A, Haloń A, Pajak J, Robaczyński J, Rabczynski J and St Gabryś M: The role of matrix metalloproteinases in tumor invasion and metastasis. Ginekol Pol. 77:63–71. 2006.(In Polish). PubMed/NCBI
34	Klein G, Vellenga E, Fraaije MW, Kamps WA and de Bont ES: The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g., acute leukemia. Crit Rev Oncol Hematol. 50:87–100. 2004. View Article : Google Scholar : PubMed/NCBI
35	Yao N, Ren K, Wang Y, Jin Q, Lu X, Lu Y, Jiang C, Zhang D, Lu J, Wang C, et al: Paris polyphylla suppresses proliferation and vasculogenic mimicry of human osteosarcoma cells and inhibits tumor growth in vivo. Am J Chin Med. 45:575–598. 2017. View Article : Google Scholar : PubMed/NCBI
36	Wang CW and Tai CJ, Choong CY, Lin YC, Lee BH, Shi YC and Tai CJ: Aqueous extract of Paris polyphylla (AEPP) inhibits ovarian cancer via suppression of peroxisome proliferator activated receptor gamma coactivator (PGC) 1alpha. Molecules. 21:7272016. View Article : Google Scholar
37	Wang W, Dong X, You L, Sai N, Leng X, Yang C, Yin X and Ni J: Apoptosis in HepaRG and HL-7702 cells inducted by polyphyllin II through caspases activation and cell-cycle arrest. J Cell Physiol. 234:7078–7089. 2019. View Article : Google Scholar : PubMed/NCBI
38	Gu L, Feng J, Xu H, Luo M and Su D: Polyphyllin I inhibits proliferation and metastasis of ovarian cancer cell line HO 8910PM in vitro. J Tradit Chin Med. 33:325–333. 2013. View Article : Google Scholar : PubMed/NCBI
39	Lou W, Chen Y, Zhu KY, Deng H, Wu T and Wang J: Polyphyllin I overcomes EMT-associated resistance to erlotinib in lung cancer cells via IL-6/STAT3 pathway inhibition. Biol Pharm Bull. 40:1306–1313. 2017. View Article : Google Scholar : PubMed/NCBI