Effects of disodium cantharidinate on dendritic cells of patients with bladder carcinoma

Zang,Guang-Hui; Li,Rui; Zhou,Rong-Sheng; Hao,Lin; He,Hou-Guang; Zhang,Wen-Da; Dong,Yang; Han,Cong-Hui

doi:10.3892/ol.2017.7589

Effects of disodium cantharidinate on dendritic cells of patients with bladder carcinoma

Authors:
- Guang-Hui Zang
- Rui Li
- Rong-Sheng Zhou
- Lin Hao
- Hou-Guang He
- Wen-Da Zhang
- Yang Dong
- Cong-Hui Han
View Affiliations

Affiliations: Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P.R. China, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China
Published online on: December 12, 2017 https://doi.org/10.3892/ol.2017.7589
Pages: 2273-2277
Copyright: © Zang 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 present study explored the effects of disodium cantharidinate (DC) on the peripheral blood-derived dendritic cells of patients with bladder carcinoma. The peripheral blood mononuclear cells from the 15 cases of urinary bladder carcinoma of middle and advanced stage were separated, and dendritic cells were prepared. The morphological changes of dendritic cells were observed. Flow cytometry was used to detect the expression levels of CD1a and CD83 on dendritic cell surface. MTT assay was utilized to measure the proliferation ability of allogeneic lymphocyte stimulated by DC. Annexin V-FITC/propidium iodide (PI) double staining flow cytometry method was carried out to detect cell apoptosis after treatment with DC. The changes in caspase-3 and PARP expression levels were investigated by western blot method. The high-dose DC resulted in a significant increase in the expressions of dendritic cell phenotyptic molecules CDla and CD83 as compared to control group. In addition, the proliferation index of allogenic lymphocyte stimulated by DC was significantly higher than that of control group. Moreover, MTT assay showed significant inhibition of the growth of BIU-87 cells. After 24 h of DC treatment, double staining flow cytometry confirmed the ability of DC to induce cell apoptosis. Further, western blot method showed a significant elevation of caspase-3 and PARP protein expression after DC treatment. In conclusion, DC treatment could induce dendritic cell maturation of patient with carcinoma of urinary bladder and promote its functional changes. Furthermore, DC was able to inhibit the proliferation of cell BIU-87 and also has the ability to induce cell apoptosis.

View Figures

View References

1	Trinchieri G and Sher A: Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 7:179–190. 2007. View Article : Google Scholar : PubMed/NCBI
2	Kawai T and Akira S: TLR signaling. Semin Immunol. 19:24–32. 2007. View Article : Google Scholar : PubMed/NCBI
3	Krieg AM: Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov. 5:471–484. 2006. View Article : Google Scholar : PubMed/NCBI
4	Inaba K, Pack M, Inaba M, Sakuta H, Isdell F and Steinman RM: High levels of a major histocompatibility complex II-self peptide complex on dendritic from the T cell areas of lymph node. J Exp Med. 186:665–672. 1997. View Article : Google Scholar : PubMed/NCBI
5	Pirtskhalaishvili G, Shurin GV, Gambotto A, Esche C, Wahl M, Yurkovetsky ZR, Robbins PD and Shurin MR: Transduction of dendritic cells with Bcl-xL increases their resistance to prostate cancer-induced apoptosis and antitumor effect in mice. J Immunol. 165:1956–1964. 2000. View Article : Google Scholar : PubMed/NCBI
6	Inoue K, Yamashita A, Yamashita M, Morioka M, Fujita Y and Terao N: Distribution of S-100 protein-positive dendritic cells inside the cancer nest and expression of HLA-DR antigen and blood group antigen on the cancer cell in transitional cell carcinoma of the urinary bladder - in relation to tumor progression and prognosis. Nihon Hinyokika Gakkai Zasshi 85: 495–503, 1994. Nihon Hinyokika Gakkai Zasshi 85: 495–503, 1994. 85: 495–503, 1994:495-503, 1994–503, 1994. 1994.(In Japanese).
7	Troy AJ, Davidson PJ, Atkinson CH and Hart DN: CD1a dendritic cells predominate in transitional cell carcinoma of bladder and kidney but are minimally activated. J Urol. 161:1962–1967. 1999. View Article : Google Scholar : PubMed/NCBI
8	Wang CC, Wu CH, Hsieh KJ, Yen KY and Yang LL: Cytotoxic effects of cantharidin on the growth of normal and carcinoma cells. Toxicology. 147:77–87. 2000. View Article : Google Scholar : PubMed/NCBI
9	Efferth T, Davey M, Olbrich A, Rücker G, Gebhart E and Davey R: Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells Mol Dis. 28:160–168. 2002. View Article : Google Scholar : PubMed/NCBI
10	Kok SH, Hong CY, Kuo MY, Lee CH, Lee JJ, Lou IU, Lee MS, Hsiao M and Lin SK: Comparisons of norcantharidin cytotoxic effects on oral cancer cells and normal buccal keratinocytes. Oral Oncol. 39:19–26. 2003. View Article : Google Scholar : PubMed/NCBI
11	McCluskey A, Ackland SP, Bowyer MC, Baldwin ML, Garner J, Walkom CC and Sakoff JA: Cantharidin analogues: Synthesis and evaluation of growth inhibition in a panel of selected tumour cell lines. Bioorg Chem. 31:68–79. 2003. View Article : Google Scholar : PubMed/NCBI
12	Verma AK and Prasad SB: Changes in glutathione, oxidative stress and mitochondrial membrane potential in apoptosis involving the anticancer activity of cantharidin isolated from redheaded blister beetles, Epicauta hirticornis. Anticancer Agents Med Chem. 13:1096–1114. 2013. View Article : Google Scholar : PubMed/NCBI
13	Li W, Xie L, Chen Z, Zhu Y, Sun Y, Miao Y, Xu Z and Han X: Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci. 101:1226–1233. 2010. View Article : Google Scholar : PubMed/NCBI
14	Chen X, Qiu J, Yang D, Lu J, Yan C, Zha X and Yin Y: MDM2 promotes invasion and metastasis in invasive ductal breast carcinoma by inducing matrix metalloproteinase-9. PLoS One. 8:e787942013. View Article : Google Scholar : PubMed/NCBI
15	Zhan YP, Huang XE, Cao J, Lu YY, Wu XY, Liu J, Xu X, Xu L, Xiang J and Ye LH: Clinical study on safety and efficacy of Qinin^® (cantharidin sodium) injection combined with chemotherapy in treating patients with gastric cancer. Asian Pac J Cancer Prev. 13:4773–4776. 2012. View Article : Google Scholar : PubMed/NCBI
16	Liu ZY, Qiu HO, Yuan XJ, Ni YY, Sun JJ, Jing W and Fan YZ: Suppression of lymphangiogenesis in human lymphatic endothelial cells by simultaneously blocking VEGF-C and VEGF-D/VEGFR-3 with norcantharidin. Int J Oncol. 41:1762–1772. 2012. View Article : Google Scholar : PubMed/NCBI
17	Shou LM, Zhang QY, Li W, Xie X, Chen K, Lian L, Li ZY, Gong FR, Dai KS, Mao YX, et al: Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of α2 integrin. Oncol Rep. 30:1059–1066. 2013. View Article : Google Scholar : PubMed/NCBI
18	Kunitani H, Shimizu Y, Murata H, Higuchi K and Watanabe A: Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in patients with chronic liver diseases. J Hepatol. 36:734–741. 2002. View Article : Google Scholar : PubMed/NCBI
19	Szabolcs P, Moore MA and Young JW: Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured with c-kit ligand, granulocyte-macrophage colony-stimulating factor, and TNF-alpha. J Immunol. 154:5851–5861. 1995.PubMed/NCBI
20	Rodríguez-Fernández JL and Corbí AL: Adhesion molecules in human dendritic cells. Curr Opin Investig Drugs. 6:1103–1111. 2005.PubMed/NCBI
21	Anguille S, Smits EL, Lion E, van Tendeloo VF and Berneman ZN: Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 15:e257–e267. 2014. View Article : Google Scholar : PubMed/NCBI
22	Collins LE, DeCourcey J, di Luca M Soledad, Rochfort KD and Loscher CE: An emerging role for SNARE proteins in dendritic cell function. Front Immunol. 6:133–139. 2015. View Article : Google Scholar : PubMed/NCBI
23	Schmitt N and Ueno H: Regulation of human helper T cell subset differentiation by cytokines. Curr Opin Immunol. 34:130–136. 2015. View Article : Google Scholar : PubMed/NCBI
24	Rouard H, Léon A, Klonjkowski B, Marquet J, Tennezé L, Plonquet A, Agrawal SG, Abastado JP, Eloit M, Farcet JP, et al: Adenoviral transduction of human ‘clinical grade’ immature dendritic cells enhances costimulatory molecule expression and T-cell stimulatory capacity. J Immunol Methods. 241:69–81. 2000. View Article : Google Scholar : PubMed/NCBI
25	Daneiger J Seager, Lutz M, Hama S, Cruz D, Castrillo A, Lazaro J, Phillips R, Prernack B and Berliner J: Method for large scale isolation, culture and cryopreservation of human monocytes suitable for ehemotaxis, cellular adhesion assays, maerophage and dendritic eell differentiation. J Immunol Methods. 288:123–134. 2004. View Article : Google Scholar : PubMed/NCBI
26	Li Z, Jo J, Jia JM, Lo SC, Whitcomb DJ, Jiao S, Cho K and Sheng M: Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell. 141:859–871. 2010. View Article : Google Scholar : PubMed/NCBI