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The anti-tumor effect of combined treatment with arsenic trioxide and interferone-α on transplanted murine Lewis lung carcinoma

Seo, Deug-Log    (College of Veterinary Medicine and Institute of Animal Medicine, Gyeongsang National University   ); Yang, Je-Hoon    (College of Veterinary Medicine and Institute of Animal Medicine, Gyeongsang National University   ); Won, Chung-Kil    (College of Veterinary Medicine and Institute of Animal Medicine, Gyeongsang National University   ); Kim, Myeong-Ok    (College of Natural Sciences, Gyeongsang National University   ); Lee, Jong-Hwan    (College of Veterinary Medicine, Konkuk University   ); Kwark, Soo-Dong    (College of Veterinary Medicine and Institute of Animal Medicine, Gyeongsang National University   ); Koh, Phil-Ok    (College of Veterinary Medicine and Institute of Animal Medicine, Gyeongsang National University  );
  • 초록

    In the present study, we expected the anti-tumor effect by combined treatment of arsenic trioxide and interferon (IFN)- ${\alpha}$ on murine Lewis lung carcinoma (LL2) cells through in vivo study. As a experimental model, LL2 cells ( $1{\times}10^{6}$ /mouse) were injected subcutaneously into the back region of mice. When the tumor volume reached $100mm^3$ , mice were treated with 1 mg/kg arsenic trioxide, 50000 IU IFN- ${\alpha}$ , or arsenic trioxide and IFN- ${\alpha}$ . The development of tumor cells was significantly inhibited by combined treatment with arsenic trioxide and IFN- ${\alpha}$ . In arsenic trioxide and IFN- ${\alpha}$ treated group, apoptotic index was reached a peak valve at 48 hr after the treatment and it was restored to approximately the control level at 8 days. Also, positive signals of Bax and Bad were increased at 48 to 96 hr and decreased at 8 day. Whereas, positive cells of Bcl-2 were steadily decreased at 12 to 48 hr and restored to the background level at 8 days. Our data showed that immunoreactivity of Bcl-2 was decreased at 12 to 48 hr, while positive signals of Bax and Bad were increased in accordance with apoptotic index at these times. In conclusion, our results suggest that the combined treatment with arsenic trioxide and IFN- ${\alpha}$ significantly inhibited the growth of LL2 tumor cells and induced apoptosis through the up and down-regulation of Bcl-2 gene family.


  • 주제어

    arsenic trioxide .   IFN- ${\alpha}$ .   apoptosis .   Bcl-2 .   Bax .   Bad.  

  • 참고문헌 (27)

    1. Oltvai ZN, Milliman CL, Korsmeryer SJ. Bcl-2 heterodimerizes in vivo with a conserved homologue, Bax, that accerates programmed cell death. Cell 1993, 74, 609-619 
    2. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QA, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY. Use of arsenic trioxide in the treatment of acute promyelocytic leukemia(APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997, 89, 3354-3360 
    3. Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ, Corso D, DeBlasio A, Gabrilove J, Scheinberg DA, Pandolfi PP, Warrell RP Jr. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 1998, 339, 1341-1348 
    4. Tallman MS. Arsenic trioxide: its role in acute promyelocytic leukemia and potential in other hematologic malignancies. Blood Rev 2001, 15, 133-142 
    5. Gutterman JU. Cytokine therapeutics: Lessons from interferon alpha. Proc Natl Acad Sci USA 1994, 91, 1198-1205 
    6. Huang SY, Chang CH, Tang JL, Tien HF, Kuo TL, Huang SF, Yao YT, Chou WC, Chung CY, Wang CH, Shen MG, Chen YC. Acute and chronic arsenic poisoning associated with treatment of acute promyelocytic leukemia. Br J Haematol 1998, 103, 1092-1095 
    7. El-Sabban ME, Nasr R, Dbaibo G, Hermine O, Abboushi N, Quignon F, Ameisen JC, Bex F, Bazarbachi A. Arsenic-interferon-alpha-triggered apoptosis in HTLV-I transformed cells is associated with tax down-regulation and reversal of NF-kappa B activation. Blood 2000, 96, 2849-2855 
    8. Zhang Y, Nie L. Studies of apoptosis of malignant lymphoma cells induced by arsenic trioxide. Cell Biol Int 2001, 25, 1003-1006 
    9. Seol JG, Park WH, Kim ES, Jung CW, Hyun JM, Lee YY, Kim BK. Potential role of caspase-3 and - 9 in arsenic trioxide-mediated apoptosis in PCI-1 head and neck cancer cells. Int J Oncol 2001, 18, 249-255 
    10. James GC, Elizabeth HR, Laura NH, Andrea JG, Steven PA, David EM, James CC, Tony RF, Russell CC, Thomas LG. Altered Bcl-2 family expression during non-genotoxic hepato-carcinogenesis in mice. Carcinogenesis 1999, 20, 1590-1599 
    11. Jing Y, Wang L, Xia L, Guo-qiang Chen GQ, Chen Z, Wilson H, Wilson M, Waxman S. Combined effect of all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia cells in vitro and in vivo. Blood 2001, 97, 264-269 
    12. Park WH, Seol JG, Kim ES, Hyun J M, Jung CW, Lee CC, Kim BK, Lee YY. Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclindependent kinase inhibitor, p21, and apoptosis. Cancer Res 2000, 60, 3065-3071 
    13. Zhu Q, Zhang JW, Zhu HQ, Shen YL, Flexor M, Jia PM, Yu Y, Cai X, Waxman S, Lanotte M, Chen DJ, Chen, Zhu, Tong JH. Synergic effects of arsenic trioxide and cAMP during acute promyelocytic leukemia cell maturation subtends a novel signaling cross-talk. Blood 2002, 99, 1014-1022 
    14. Real FX, Oettgen HF, Krown SE. Kaposi's sarcoma and the equired immunodefeciency syndrome : treatment with high and low doses of recombinant leukocyte a interferon. J Clin Oncol 1986, 4, 544-551 
    15. Jing Y, Dai J, Ruth ME, Chalmers-Redman, Willam G, Willam T, Waxman S. Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a Hydrogen peroxide-dependent pathway. Blood 1999, 94, 2102-2111 
    16. Nasr R, Rosenwald A, El-Sabban ME, Arnulf B, Zalloua P, Lepelletier Y, Bex F, Hermine O, Staudt L, Bazarbachi A. Arsenic/interferon specifically reverses 2 distinct gene networks critical for the survival of HTLV-1-infected leukemic cells. Blood 2003, 101, 4576-4582 
    17. Maurizio G, Marcel HM, Koken MK, Chelbi A, Gerard B, Michel L, Chen Z, de The H. Combined arsenic and retinoic acid treatment enhances differentiation and apoptosis in arsenic-resistant NB4 cells. Blood 1998, 91, 4300-4310 
    18. Zhao W, Wang H, Wu F, Guo W, Qu B, Shen Z, Wang Z. Effects of All-trans-retinoic acid and Arsenic trioxide on the hemostatic disturbance associated with acute promyelocytic leukemia. Thromb Res 2001, 102, 197-204 
    19. Chen GQ, Shi XG, Tang W, Xiong SM, Cai X, Han ZG, Ni JH, Shi GY, Jia PM. Liu MM, He KL, Niu C, Ma J, Zhang P, Zhang TD, Paul P, Naoe T, Kitamura K, Miller W, Waxman S, Wang ZY, Chen SJ, Chen Z. Use of arsenic trioxide in the treatment of acute promyelocytic leukemia(APL): I. $As_2O_3$ experts dose- dependent dual effects on APL cells. Blood 1997, 89, 3345-3353 
    20. Ezekowitz RAB, Mulliken JB, Folkman J. Interferon alpha2 a therapy for life threatening hemangiomas of infancy. N Engl J Med 1992, 326, 1456-1463 
    21. Bursch W, Lauer B, Timmerman-Trosiener L, Barthel G, Schuppler J, Sculte-Hermann R. Controlled cell death(apoptosis) of normal and putative neoplastic cells in rat liver following withdrawal of tumor promoters. Carcinogenesis 1984, 5, 53-58 
    22. Kito M, Akao Y, Ohishi N, Yagi K, Nozawa Y. Arsenic trioxide-induced apoptosis and its enhancement by buthionine sulfoximine in hepatocellular carcinoma cell lines. Biochem Biophys Res Commun 2002, 291, 861-867 
    23. Schulte-Hermann R, Timmerman-Trosnier I, Barthel G. Bursch W. DNA synthesis, apoptosis and phenotypic expression as determinants of growth altered foci in rat liver during phenobarbital promotion. Cancer Res. 1990, 50, 5127-5135 
    24. Yuksel S, Saydam G, Uslu R, Sanli UA, Terzioglu E, Buyukececi F, Omay SB. Arsenic trioxide and methylprednisolone use different signal transduction pathways in leukemic differentiation. Leuk Res 2002, 26, 391-398 
    25. Brocheriou I, Carnot F, Briere J. Immunohistochemical detection of Bcl-2 protein in thymoma. Histopathology 1995, 27, 251-255 
    26. White CW, Sondheimer HM, Crouch EC, Wilson H, Fan LL. Treatment of pulmonary hemangiomatosis with recombinant interferon alpha-2a. N Engl J Med 1989, 320, 1197-1200 
    27. Bachleitner-Hofmann T, Gisslinger B, Grumbeck E, Gisslinger H. Arsenic trioxide and ascorbic acid: synergy with potential implications for the treatment of acute myeloid leukemia. Br J Haematol 2001, 112, 783-786 

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