Reversal effect of Ganoderma lucidum polysaccharide on multidrug resistance in K562/ADM cell line1
Corresponding Author
Wei-dong LI
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Correspondence to Prof Wei-dong LI. Phn 86-10-8280-2798. Fax 86-10-8280-1686. E-mail [email protected]Search for more papers by this authorBo-di ZHANG
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Search for more papers by this authorRan WEI
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Search for more papers by this authorJi-hong LIU
Confocal Microscope Laboratory, Peking University Health Science Center, Beijing 100083, China
Search for more papers by this authorZhi-bin LIN
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Search for more papers by this authorCorresponding Author
Wei-dong LI
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Correspondence to Prof Wei-dong LI. Phn 86-10-8280-2798. Fax 86-10-8280-1686. E-mail [email protected]Search for more papers by this authorBo-di ZHANG
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Search for more papers by this authorRan WEI
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Search for more papers by this authorJi-hong LIU
Confocal Microscope Laboratory, Peking University Health Science Center, Beijing 100083, China
Search for more papers by this authorZhi-bin LIN
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China
Search for more papers by this authorThis research was supported by a research fund from Shanghai Green Valley Holding.
Abstract
Aim: To investigate the reversal effect of Ganoderma lucidum polysaccharides (Gl-PS) on multidrug resistance (MDR) in the adriamycin (ADM)-resistant leukemic cell line K562/ADM. Methods: Cytotoxicity was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method; the ADM concentration in cells was determined by flow cytometry and confocal laser scanning microscopy techniques; the expression of P-glycoprotein was assayed by flow cytometry; and the mRNA expression levels of MDR-1 and MDR-associated protein (MRP)1 were determined by RT-PCR Results:Gl-PS reversed MDR in K562/ADM cells. Gl-PS obviously reversed the resistance of K562/ADM to doxorubicin. The reversing factors of Gl-PS at 10 and 20 mg/L were 6.46 and 6.80, respectively. MDR-1 and MRP 1 transcription were downregulated by 10 and 50 mg/L Gl-PS. Conclusion:Gl-PS can reverse the MDR by downregulating the expression of MDR-1 and MRP1 in K562/ADM cells.
References
- 1 Goldstein LJ. MDR1 gene expression in solid tumors. Eur J Cancer 1996; 32: 1039–50.
- 2 Jonker JW, Buitelaar M, Wagenaar E. The breast cancer resistance protein protects against a major chlorophy11-derived dietary phototoxin and protoporphyria. Proc Natl Acal Sci USA 2002; 99: 15649–54.
- 3 Johnstone RW, Ruefli AA, Lowe SW. Apoptosis: a line between cancer genetics and chemotherapy. Cell 2002; 108: 153–64.
- 4 Shen DW, Cardarelli C, Hwang J, Cornwell M, Richert N, Ishii S, et al. Multiple drug-resistant human KB carcinoma cells independently selected for high-level resistance to colchicines, adriamycin, or vinblastine show changes in expression of specific proteins. J Biol Chem 1986; 261: 7762–70.
- 5 Tan B, Piwnica WD, Rater L. Multidrug resistance transporters and modulation. Curr Opin Oncol 2000; 12: 450–8.
- 6 Sharom FJ, Yu X, Lu P, Liu P, Chu JW, Szabo K, et al. Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems and intact cells. Biochem Pharmacol 2003; 58: 571–86.
- 7 Sikic BI. Modulation of multidrug resistance: a paradigm for translational clinical research. Oncology 1999; 13: 183–7.
- 8 Hu YP, Pourquier P, Doignon F, Crouzet M, Robert J. Effects of modulators of multidrug resistance on the expression of the MDR1 Gene on human KB cells in culture. Anticancer Drugs 1996; 7: 738–44.
- 9 Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhancedcytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 1981; 41: 1967–72.
- 10 Lei LS, Lin ZB. Effects of Ganoderma polysaccharides on the activity of DNA polymerase in spleenocytes and immune function in aged mice. Acta Pharm Sin 1993; 28: 577–82.
- 11 Zhang QH, Lin ZB. The antitumor avtivity of Ganoderma lucidum (Curt:Fr.) P. Karst. (LingZhi) (Aphyllophoromycetideae) polysaccharides is related to tumor necrosis factor-α and interferon-γ. Int J Med Mushroom 1999; 1: 207–15.
- 12 Lin ZB. Anti-aging activities of Ganoderma lucidum. In ZB Lin, editor. 2007. Modern research of Ganoderma. 3rd ed. Beijing : Beijing Medical University Publishing House; 2007. p 241–2.
- 13 Chen HS, Lin CH, Wong CH. Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum polysaccharides. Bioorg Med Chem 2004; 12: 5595–601.
- 14 Zhang QH, Lin ZB. Study on antitumor activity and mechanism of Ganoderma polysaccharides B. Chin J Integrated Tradit West Med 1999; 19: 544–7.
- 15 Zhang QH, Yu DH, Lin ZB. Study on the antitumor mechanism of ganoderma lucidum extract (gle) by serologic pharmacological method. J Beijing Med Univ 2000; 32: 210–3.
- 16 Hu YH, Lin ZB, He YQ, Zhao CJ. Polysaccharides isolated from mycelia of ganoderma lucidum induced on hl-60 cell apoptosis by enhancing macrophage activity. Chin Pharmacol Bull 1999; 15: 27–30.
- 17 Sliva D, Labarrere C, Slivova V, Sedlak M, Lloyd FPJ, Ho NW. Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells. Biochem Biophy Res Commun 2002; 298: 603–12.
- 18 Lei LS, Lin ZB, Chen Q, Li RZ, He YQ. Antagonistic effect of ganoderma lucidum polysaccharides on the immunosuppressive response induced by ciclosporin a, hydrocortisone and antitumor agents. Chin J Pharmacol Toxicol 1994; 7: 183–5.
- 19 Li WD, Han Q, Lin ZB. Antagonization of ganoderma polysaccharides and lentinan on bearing sarcoma 180 mice's immunosuppressive effect induced by cyclophosphamide. Chin J Integt Trad West Med 2001; 21(Suppl): 101–4.
- 20 Lin ZB, Zhang HN. Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta Pharmacol Sin 2004; 25: 1387–95.
- 21 Alley MC, Scudiero DA, Monks A. Feasibility of drug screening with panels of human tumour cell lines using a microculture tetrazolium assay. Cancer Res 1988; 48: 589–601.
- 22 Barhoumi R, Bailey RH, Burghardt RC. Kinetic analysis of glutathione in anchored cells with monochlorobimane. Cytometry 1995; 19: 226–34.
- 23 Minderman H, Suvannasankha A, O'Loughlin KL, Scheffer GL, Scheper RJ, Robey RW, et al. Flow cytometric analysis of breast cancer resistance protein expression and function. Cytometry 2002; 48: 59–65.
- 24 Cao QZ, Lin ZB. Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide. Acta Pharmacol Sin 2004; 25: 833–8.
- 25 Jeanette W, Jan CD. Involvement of multidrug resistance proteins (P-gp) and in the modulation of glucocorticoid response. J Steroid Biochem Mol Biol 2002; 82: 277–88.
- 26 Miao ZH, Ding J. Transcription factor c-Jun activation represses mdr-1 gene expression. Cancer Res 2003; 63: 4527–32.
