Reversal effect and mechanism of Ginkgo biloba exocarp extracts in multidrug resistance of mice S180 tumor cells

Hu,Bi‑Yuan; Gu,Yun‑Hao; Cao,Chen‑Jie; Wang,Jun; Han,Dong‑Dong; Tang,Ying‑Chao; Chen,Hua‑Sheng; Xu,Aihua

doi:10.3892/etm.2016.3589

Reversal effect and mechanism of Ginkgo biloba exocarp extracts in multidrug resistance of mice S180 tumor cells

Authors:
- Bi‑Yuan Hu
- Yun‑Hao Gu
- Chen‑Jie Cao
- Jun Wang
- Dong‑Dong Han
- Ying‑Chao Tang
- Hua‑Sheng Chen
- Aihua Xu
View Affiliations

Affiliations: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co‑Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China
Published online on: August 11, 2016 https://doi.org/10.3892/etm.2016.3589
Pages: 2053-2062
Copyright: © Hu 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 aim of the present study was to investigate the reversal effect and its related mechanism of Ginkgo biloba exocarp extracts (GBEEs) in obtained multidrug resistance (MDR) of mice S180 tumor cells in vitro and in vivo. In order to simulate the clinical PFC [cis‑dichlorodiamineplatinum, cisplatin (DDP) + fluorouracil (FU), FU+cyclophosphamide and cyclophosphamide] scheme, a gradually increasing dose was administered in a phased induction in order to induce S180 cells in vivo and to make them obtain multidrug resistance. The results in vitro demonstrated that GBEE could significantly increase the IC50 of DDP on S180 MDR cells, increase the accumulation of Adriamycin (ADR) and rhodamine 123 (Rho 123), and reduce the efflux of Rho 123 of S180 MDR cells. The results from the in vivo treatment with a combination of GBEE and DDP to S180 MDR ascites tumor in mice demonstrated that each dose of GBEE could effectively reverse the drug‑resistance of S180 MDR cells to DDP in order to extend the survival time of mice with ascite tumors and inhibit tumor growth in solid tumor mice. In addition, GBEE effectively inhibited the expression of MDR‑1 mRNA and multidrug resistance‑associated protein‑1 mRNA in S180 MDR cells of ascites tumor in mice and improved the expression levels of cytokines, including interleukin (IL)‑3, IL‑18 and interferon‑γ in the blood serum of S180 MDR tumor‑bearing mice. The present study showed that the mechanism of GBEE reversal of MDR may be associated with the inhibition of the functional activity of P‑glycoprotein, the downregulation of drug resistance related gene expression of S180 MDR cells and the improvement of the production of related serum cytokines of S180 MDR tumor mice.

View Figures

View References

1	Daniel C, Bell C, Burton C, Harguindey S, Reshkin SJ and Rauch C: The role of proton dynamics in the development and maintenance of multidrug resistance in cancer. Biochim Biophys Acta. 1832:606–617. 2013. View Article : Google Scholar : PubMed/NCBI
2	Huang F, Wu XN, Chen J, Wang WX and Lu ZF: Resveratrol reverses multidrug resistance in human breast cancer doxorubicin-resistant cells. Exp Ther Med. 7:1611–1616. 2014.PubMed/NCBI
3	Molinas A, Sicard G and Jakob I: Functional evidence of multidrug resistance transporters (MDR) in rodent olfactory epithelium. PLoS One. 7:e361672012. View Article : Google Scholar : PubMed/NCBI
4	Wu F, Shao ZY, Zhai BJ, Zhao CL and Shen DM: Ultrasound reverses multidrug resistance in human cancer cells by altering gene expression of ABC transporter proteins and Bax protein. Ultrasound Med Biol. 37:151–159. 2011. View Article : Google Scholar : PubMed/NCBI
5	Dean M, Hamon Y and Chimini G: The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res. 42:1007–1017. 2001.PubMed/NCBI
6	Wan X and Sun G: The research progress of immune mechanism of reverse tumor multi-drug resistance. An Hui Yi Yao. 10:401–402. 2006.(In Chinese).
7	Gomes-Giacoia E, Miyake M, Goodison S, Sriharan A, Zhang G, You L, Egan JO, Rhode PR, Parker AS, Chai KX, et al: Intravesical ALT-803 and BCG treatment reduces tumor burden in a carcinogen induced bladder cancer rat model; a role for cytokine production and NK cell expansion. PLoS One. 9:e967052014. View Article : Google Scholar : PubMed/NCBI
8	Johnson SD, De Costa AM and Young MR: Effect of the premalignant and tumor microenvironment on immune cell cytokine production in head and neck cancer. Cancers (Basel). 6:756–770. 2014. View Article : Google Scholar : PubMed/NCBI
9	Zhen JH: Progress in research on interleukin −2. Strait Pharmaceutical Journal. 18:1–3. 2006.
10	Liu YL, Chen TG and Liu XL: Research progress of interferon. Progress in Veterinary Medicine. 29:81–84. 2008.
11	Fu S and Qian YK: Research progress of tumor necrosis factor. International Journal of Immunology. 5:252–257. 1993.
12	Tu WQ and Yang XQ: Regulation of cytokine immune response and its clinical significance. Foreign Medical Sciences(Section of Pediatrics). 5:228–232. 1993.
13	Cun YM, Yang YX, Xiang Y, et al: IL-2 gene transfection reversing multidrug resistance in choriocarcinoma cell line. Basic and Clinical Medicine. 21:523–526. 2001.
14	Hu JW, Shen ZY, Yang JC, et al: Combination of interferon gamma and Vera Pammy to reverse multidrug resistance in human lung cancer cell line. Suzhou University Journal of Medical Science. 23:16–18. 2003.
15	Malorni W, Rainaldi G, Tritarelli E, et al: Tumor necrosis factor alpha is a powerful apoptotic inducer in lymphoid leukemic cells expressing the P-170 glycoprotein. International Journal of Cancer. 67:238–47. 1996. View Article : Google Scholar : PubMed/NCBI
16	Chen X, Fu L and Liu Z: Reversal of multidrug resistance in cancer cell by verapamil: A research progress. Foreign Medical Science (Section of Pharmacy). 34:190–193. 2007.(In Chinese).
17	Jiao B: Experimental study of reversal of multidrug resistance by cyclosporin a in various human gliom cell lines. Zhong Liu Fang Zhi Yan Jiu. 28:457–459. 2001.(In Chinese).
18	Xu AH, Chen HS and Zhuo C: The inhibitory effect of Ginkgo biloba endocarp polysaccharides (GBEP) on human cancer cell strains and its synergic effect in combination with adriamycin. Zhong Guo Xin Yao Za Zhi. 9:753–755. 2000.(In Chinese).
19	Chen Y, Mao LL, Hu BY, Chen HS and Xu AH: Synergistic attenuated antitumor effect of Ginkgo biloba exocarp extracts combined with cis-dichlorodiamineplatinum in S180 tumor-bearing mice. Zhong Guo Xin Yao Za Zhi. 23:1569–1573. 2014.(In Chinese).
20	Xu AH, Ren L, Zheng YY and Chen HS: Immunomodulatory effect of Ginkgo biloba exocarp polysaccharides on immunosuppressive mice induced by cyclophosphamide. Zhong Guo Yao Li Xue Yu Du Li Xue Za Zhi. 22:69–72. 2008.(In Chinese).
21	Chen HS, Zhuo F and Chu YF: Clinical study on treatment of patients with upper digestive tract malignant tumors of middle and late stage with Ginkgo biloba exocarp polysaccharides capsule preparation. Zhong Xi Yi Jie He Xue Bao. 1:189–191. 2003.(In Chinese). View Article : Google Scholar : PubMed/NCBI
22	Zhai F and Chen HS: Ginkgo biloba exocarp Polysaccharide preparation in the treatment of 84 cases of advanced cancer. Liao Ning Zhong Yi Za Zhi. 29:5642002.
23	Shen TT, Xu AH, Zheng YY, et al: Anti-metastasis effect of Ginkgo biloba exocarp extracts on metastasis of Lewis lung cancer in C57BL /6J mice and its mechanism. Chin J of Pharmacol Toxicol. 27:67–71. 2013.
24	Xu JL, Wang ZH and FJ S: Establishment of tumor multi-drug resistance mice model induced by combination chemotherapeutic in vivo. Shi Yan Dong Wu Yu Bi Jiao Yi Xue. 25:215–217. 2005.
25	Chen Q, Li GH and Sun FJ: Establishment of obtained multidrug resistance model of S180 cell line mice used for study on Chinese materia medica and its stability. Zhong Cao Yao. 37:1691–1694. 2006.(In Chinese).
26	Wu Q, Xu A, Yang Q, Wang LX and Chen HS: Influence of effective part GBEE-2 of exocarpium ginkgo extracts on apoptosis and apoptotic pathway of human gastric adenocarcinoma cell line SGC-7901. Traditional Chinese Drug Research and Clinical Pharmacology. 22:270–273. 2011.
27	Cao CJ: Inhibitory effect of extract of Ginkgo biloba extract on liver cancer in mice and its effect on survivin expression. Shi Zhen Guo Yi Guo Yao. 26:1322–1324. 2015.
28	Zrieki A, Farinotti R and Buyse M: Cyclooxygenase-2 inhibitors prevent trinitrobenzene sulfonic acid-induced P-glycoprotein up-regulation in vitro and in vivo. Eur J Pharmacol. 636:189–197. 2010. View Article : Google Scholar : PubMed/NCBI
29	Loetchutinat C, Saengkhae C, Marbeuf-Gueye C and Garnier-Suillerot A: New insights into the P-glycoprotein-mediated effluxes of rhodamines. Eur J Biochem. 270:476–485. 2003. View Article : Google Scholar : PubMed/NCBI
30	Xu SY, Bian RL and Chen X: Screening method of animal tumor in vivoExperimental Methodology of Pharmacology. 3rd. People's Medical Publishing House; Beijing: pp. 1757–1784. 2002
31	Isabel D, Ferreira I, Virgílio E, do Rosário I and Pedro VL: Cravo* 2: Real-time quantitative PCR with SYBR Green I detection forestimating copy numbers of nine drug resistance candidate genes in Plasmodium falciparum. Malaria Journal. 5:1–6. 2006. View Article : Google Scholar : PubMed/NCBI
32	Zhang Y, Jia YJ and Li XJ: Resistance reversal effect of astragalus polysaccharides for injection on cisplatin-resistant human lung adenocarcinoma cell line A549/DDP. Drug Evaluation Research. 35:417–419. 2012.(In Chinese).
33	Wu HY, Chen YM, Lin L, Qiu QA and Liu N: Lentinan enhances cisplatin-mediated inhibition of cell proliferation in human gastric cancer cell line SGC-7901. Shi Jie Hua Ren Xiao Hua Za Zhi. 19:344–348. 2011.(In Chinese).
34	Li ZH, An C, Hu KW, Zhou KH, Duan HH and Tang MK: Multidrug resistance reversal activity of total alkaloid from Fritillaria thunbergii on cisplatin-resistant hum an lung adenocarcinom a A549/DDP cells. Zhong Guo Yao Li Xue Yu Du Li Xue Za Zhi. 27:315–320. 2013.(In Chinese).
35	Zhu C, Liu XF and Li G: Effect of Brucea Javanica oil emulsion combined with adramycin for refractory malignant pleural effusion. Shi Yong Quan Ke Yi Xue. 5:871–873. 2007.(In Chinese).
36	Hennessy M and Spiers JP: A primer on the mechanics of P-glycoprotein the multidrug transporter. Pharmacol Res. 55:1–15. 2007. View Article : Google Scholar : PubMed/NCBI
37	Kruh GD and Belinsky MG: The MRP family of drug efflux pumps. Oncogene. 22:7537–7552. 2003. View Article : Google Scholar : PubMed/NCBI
38	Peng YM, Wang N, Wang YF, Han L, Zhang Y, Jiang JH, Zhou YB and Wang QD: Correlation between reversing effect of cepharanthine hydrochloride on multidrug resistance and P-glycoprotein expression and function of K562/ADR cells. Yao Xue Xue Bao. 47:594–599. 2012.(In Chinese). PubMed/NCBI
39	Niethammer AG, Wodrich H, Loeffler M, Lode HN, Emmerich K, Abdollahi A, Krempien R, Debus J, Huber PE and Reisfeld RA: Multidrug resistance-1 (MDR-1): A new target for T cell-based immunotherapy. FASEB J. 19:158–159. 2005.PubMed/NCBI
40	Shi YJ, Ren HY, Cen XN, Zhu Q and Yu JR: Immunological effector cells enhance apoptosis induced by adriamycin in a multi-drug resistant human breast cancer cell line. Zhonghua Zhong Liu Za Zhi. 28:188–191. 2006.(In Chinese). PubMed/NCBI
41	Wang L, Deng Q, Wang J, Bai X, Xiao X, Lv HR, Zhao MF and Liu PJ: Effect of CIK on multidrug-resistance reversal and increasing the sensitivity of ADR in K562/ADR cells. Oncol Lett. 8:1778–1782. 2014.PubMed/NCBI
42	Ping CQ, Zhang YJ, Sun GX, Dong M, Zhou XL, Ping J, Liu Y Qm and Hong LJ: The expression effect of DC-CIK on K562/A multidrug resistance gene mdr1. Xian Dai Sheng Wu Yi Xue Jin Zhan. 14:2667–2671. 2014.(In Chinese).
43	Wang CH, Pan CX and Wang W: The reversal study of alpha-interferon on human breast cancer multidrug resistance cell lines MX-1/Taxo (MX-1/T). Dang Dai Yi Xue. 20:17–19. 2014.(In Chinese).
44	Li Y, Zou Y, Cai B, Yang B, Ying B, Shi Y and Wang L: The associations of IL-18 serum levels and promoter polymorphism with tacrolimus pharmacokinetics and hepatic allograft dysfunction in Chinese liver transplantation recipients. Gene. 491:251–255. 2012. View Article : Google Scholar : PubMed/NCBI
45	Yu CF, Hong JH and Chiang CS: The roles of macrophages and nitric oxide in interleukin-3-enhanced HSV-Sr39tk-mediated prodrug therapy. PLoS One. 8:e565082013. View Article : Google Scholar : PubMed/NCBI
46	Li J, Fu EC, Xu AH, et al: Effect of GBEE on the levels of IL-2, IL-12, TNF- and TGF- in tumor bearing mice. Chinese Journal of Immunology. 28:415–417. 2012.