Effects of AZT and RNA-protein complex (FA-2-b-beta) extracted from Liang Jin mushroom on apoptosis of gastric cancer cells.

Yan-Qing Sun, Tian-Kang Guo, Ya-Ming Xi, Che Chen, Jin Wang, Zi-Ren Wang
Author Information
  1. Yan-Qing Sun: School of Life Science, Lanzhou University, Lanzhou 730000, Gansu Province, China.

Abstract

AIM: To investigate the synergistic effects of 3'-azido-3'-deoxythymidine (AZT) and FA-2-b-beta extracted from Ling Jin mushroom on apoptosis of gastric cancer cells MKN45 in vitro.
METHODS: MTT analysis was made to examine the inhibition rate of MKN45 cells treated with AZT (2.5, 5, 10 and 20 mg/L) and FA-2-b-beta (5, 10, 20 and 40 mg/L) singly and combinatively for 24, 48 and 72 h. Apoptotic effects were evaluated by morphological methods, DNA agarose gel electrophoresis and flow cytometry, respectively. Telomerase activity was estimated by TRAP-ELISA. The mRNA expression of caspase-3 and Bcl-2 were detected by RT-PCR.
RESULTS: AZT and FA-2-b-beta could significantly inhibit MKN45 cell proliferation and induce its apoptosis. MKN45 cells were inhibited in dose- and time- dependent manner. The inhibition effect of AZT combined with FA-2-b-beta was obviously better than that used singly (0.469 +/- 0.022 vs 1.075 +/- 0.055, P < 0.05, 0.325 +/- 0.029 vs 0.469 +/- 0.022 P < 0.01). AZT used singly and combination of FA-2-b-beta could decrease the activity of tumor cell telomerase, and AZT has synergistic function with FA-2-b-beta. A certain concentration of AZT could up-regulate the expression of caspase-3 mRNA (r = 0.9969, P < 0.01), which was positively related to apoptosis rate, and could down-regulate the expression of Bcl-2 mRNA, which was negatively related to apoptosis rate (r = 0.926, P < 0.01). Furthermore, the effect of AZT combined with FA-2-b-beta was significantly higher than that used singly.
CONCLUSION: Combination of AZT and FA-2-b-beta has an obviously synergetic effect in the gastric cancer cells MKN45, which has provided a new approach to the treatment of gastric cancer clinically.

References

  1. Cell. 1997 Aug 22;90(4):785-95 [PMID: 9288757]
  2. World J Gastroenterol. 2003 Sep;9(9):1930-4 [PMID: 12970878]
  3. Carbohydr Res. 1989 Mar 15;186(2):267-73 [PMID: 2736561]
  4. J Surg Res. 2006 Apr;131(2):252-5 [PMID: 16427084]
  5. Biol Pharm Bull. 2004 Mar;27(3):404-6 [PMID: 14993810]
  6. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):10964-7 [PMID: 10500109]
  7. Nat Rev Drug Discov. 2006 Jul;5(7):577-84 [PMID: 16773071]
  8. Arch Pathol Lab Med. 1998 Apr;122(4):310-9 [PMID: 9648897]
  9. Biochem Pharmacol. 1990 Nov 15;40(10):2353-62 [PMID: 2244936]
  10. Blood. 2006 Aug 1;108(3):1021-9 [PMID: 16569765]
  11. Shock. 2006 Apr;25(4):420-5 [PMID: 16670646]
  12. Cancer Res. 2003 Feb 15;63(4):824-30 [PMID: 12591733]
  13. Int J Gynecol Cancer. 2004 Jul-Aug;14(4):589-94 [PMID: 15304151]
  14. Science. 1994 Dec 23;266(5193):2011-5 [PMID: 7605428]
  15. J Biol Chem. 1997 May 30;272(22):14183-7 [PMID: 9162048]
  16. Pharmacol Toxicol. 2000 Sep;87(3):138-43 [PMID: 11068855]
  17. J Agric Food Chem. 2004 Oct 6;52(20):6330-7 [PMID: 15453709]
  18. Biochem Biophys Res Commun. 1998 May 8;246(1):107-10 [PMID: 9600076]
  19. J Nutr. 2001 May;131(5):1409-13 [PMID: 11340091]
  20. Curr Opin Oncol. 2004 Jan;16(1):32-8 [PMID: 14685090]
  21. Leukemia. 2002 Apr;16(4):433-43 [PMID: 11960320]
  22. DNA Cell Biol. 2004 Mar;23(3):135-40 [PMID: 15068582]
  23. Biosci Biotechnol Biochem. 2005 Dec;69(12):2466-9 [PMID: 16377912]
  24. Nature. 1998 Jan 1;391(6662):43-50 [PMID: 9422506]
  25. Jpn J Clin Oncol. 1997 Aug;27(4):216-20 [PMID: 9379506]
  26. Breast Cancer Res Treat. 2005 Oct;93(3):227-36 [PMID: 16132531]
  27. Clin Cancer Res. 1998 Mar;4(3):693-6 [PMID: 9533539]
  28. Toxicol In Vitro. 2005 Jun;19(4):533-9 [PMID: 15826811]
  29. Cell Struct Funct. 2001 Apr;26(2):103-8 [PMID: 11482452]
  30. Biochem Biophys Res Commun. 2007 Mar 9;354(2):351-6 [PMID: 17223082]

MeSH Term

Agaricales
Apoptosis
Caspase 3
Cell Line, Tumor
Cell Proliferation
Dose-Response Relationship, Drug
Drug Synergism
Drug Therapy, Combination
Drugs, Chinese Herbal
Gene Expression Regulation, Neoplastic
Humans
Phytotherapy
Plant Proteins
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger
Stomach Neoplasms
Zidovudine

Chemicals

Drugs, Chinese Herbal
Plant Proteins
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger
Zidovudine
Caspase 3

Word Cloud

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