Maxillofacial Plastic and Reconstructive Surgery

  • 제29권5호
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  • Pages.394-404
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  • 2007
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  • 2288-8101(pISSN)
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  • 2288-8586(eISSN)
대한악안면성형재건외과학회 (Korean Association of Maxillofacial Plastic and Reconstructive Surgeons)
권호 표지

구강 편평세포암종에서 Taxol과 Cyclosporin A의 세포사멸 상승 작용 효과

SYNERGISTIC APOPTOTIC EFFECT OF TAXOL ON ORAL SQUAMOUS CELL CARCINOMA BY CYCLOSPORIN A

  • 서민정 (단국대학교 치과대학 구강악안면외과학교실) ;
  • 한세진 (단국대학교 치과대학 구강악안면외과학교실) ;
  • 이재훈 (단국대학교 치과대학 구강악안면외과학교실)
  • Suh, Min-Jung (Department of Oral and Maxillofacial Surgery, School of Dentistry, Dankook University) ;
  • Han, Se-Jin (Department of Oral and Maxillofacial Surgery, School of Dentistry, Dankook University) ;
  • Lee, Jae-Hoon (Department of Oral and Maxillofacial Surgery, School of Dentistry, Dankook University)
  • 발행 : 2007.09.30
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초록

Oral squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its high metastasis and recurrent rates and poor prognosis. Taxol is an anticancer agent which is microbial products extracted from jew tree. It combines with the tubulin and induces apoptosis by inhibiting mitosis of cell with microtubule stabilization. Recently, it was reported to be effective in various solid tumors, but only very slight effect has been seen in oral squamous cell carcinomas due to its cell-specific potencies. Cyclosporin A is used as immune suppressant and is being applied in anticancer therapy as its mechanism of induction of change of apoptotic process in various cells have been known. In this study, oral squamous cell carcinoma HN22 cell line was used for in vitro experiment and as for the experimental group taxol and cyclosporin A were applied alone and to observe the synergistic effect of apoptosis, Taxol and cyclosporin A were coadministered with different concentration of taxol for comparison. The results were obtained as follow: 1. There was no difference in Bcl-2, Bax, caspase 3, 8, 9 mRNA expression when cyclosprin A or taxol was applied alone to HN 22 cell line. 2. Caspase 3, 9 mRNA expression was prominently increased when cyclosprin A and taxol were applied together to cancer cell. 3. No significant difference was observed when cyclosporin A and taxol($1{\mu}g/ml$ and $3{\mu}g/ml$) were applied together to cancer cell line. 4. No significant difference was seen in Bcl-2, Bax, and caspase 8 mRNA expression in all the groups of in vitro experiments. 5. When cyclosporin A was applied alone in vivo study on the nude mice, histopathologi cal findings was similar to those of the control group. Oral squamous cell carcinoma induced by inoculation of HN 22 cell line was not reduced after treatment of cyclosporin A. 6. When taxol was applied alone, the islands of squamous cell carcinoma still remained, which meant insignificant healing effect. There was a lesser volume increase compared with the cyclosporin A alone. 7. When taxol and cyclosporin A were applied together, the connective tissue and calcification were seen in the histopathologic findings. Oral squamous cell carcinoma was decreased and cancer cell was disappeared. In observing the tumor mass change with time, there was a gradual decreased size and healing features. As the results of the in vitro experiment, it could conclud that only when the two agents are applied together, mitochondria-mediated apoptosis occurred by considerable increase of caspase 3, 9 mRNA expression, irrespectable of the concentration of taxol. In vivo experiment, there was a discrete synergistic effect when the two agents were applied together. But single use of cyclosporin A was not effective in this study. Based on the results of this experiment, if further clinical studies are done, taxol and cyclosporin A could be effectively used in treatment of oral squamous cell carcinomas.

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참고문헌

  1. Vikran B, Strong E, Shah J et al : Failure at the primary site-following multimodality treatment for advanced head and neck cancer. Head Neck Surg 6 : 720, 1984 https://doi.org/10.1002/hed.2890060303
  2. Peterson LJ : Principles of oral and maxillofacial surgery. Philadelphia, J.B. Lippincott, 1992
  3. Wani MC, Taylor HL, Wall ME : Plant antitumor agents VI, The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 893 : 2325, 1971
  4. Yvon A, Wadsworth P, Jordan MA : Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol Biol Cell 10(4) : 947, 1999 https://doi.org/10.1091/mbc.10.4.947
  5. Rowinsky EK : The development and clinical utility of the taxan class of antimicrotubule chemotherapy a gents. Annu Rev Med 48 : 353, 1997 https://doi.org/10.1146/annurev.med.48.1.353
  6. Rowinsky EK, Cazenave LA, Donehower RC : Taxol ; a novel investigational antimicrotuble agent. Nat Cancer Inst 82 : 1247, 1999
  7. Schiff PB, Fant J, Horwitz SB : Promotion of microtubule assembly in vitro by taxol. Nature 277 : 665, 1979 https://doi.org/10.1038/277665a0
  8. Schiff PB, Horwitz SB : Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl cad Sci USA 77 : 1561, 1980
  9. Manfredi J, Horwitz SB : Taxol ; An antimitotic agents with a new mechanism of action. Pharmcol Ther 25 : 83, 1984 https://doi.org/10.1016/0163-7258(84)90025-1
  10. Jordan MA, Wendell KL, Gardiner S et al : Mitotic block induce in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res 56 : 816, 1996
  11. Jordan MA, Wilson L : Microtubules and actin filaments :dynamic targets for cancer chemotherpy. Curr Opin Cell Biol 10(1) : 123, 1998 https://doi.org/10.1016/S0955-0674(98)80095-1
  12. Ahn HJ, Kim YS, KIm YU et al : Mechanism of taxol induced apotosis in human SKOV2 ovarian carcinoma cells. J cellular Biochem 91 : 1043, 2004 https://doi.org/10.1002/jcb.20006
  13. Ofir R, Seiman R, Rabinski T et al : Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent. Cell Death Differ 9(6) : 636, 2002 https://doi.org/10.1038/sj.cdd.4401012
  14. Mcmorris TC, Estes Kelner MJ, L, et al : Noneresponsiveness of the metastatic human lung carcinoma MV522 xenograft to conventional anticancer agents. Anticancer Res 15 : 867, 1995
  15. Rowinsky EK, Donehower RC, Jones RJ et al : Microtubule changes and cytotoxicity in leukemic cell lines treated withtaxol. Cancer Res 49 : 4093, 1988
  16. Haldar S, Jena N, Croce CM : Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA 9b : 92(10) : 4507, 1995
  17. Wang TH, Popp DM, Wang HS et al : Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c-Jun N-terminal Kinase(JNK)-dependent and independent pathways in ovarian cancer cell. J Biol Chem 274(12) : 8208, 1999 https://doi.org/10.1074/jbc.274.12.8208
  18. Lu KH, Leu K, Liao HH et al : Induction of caspase - 3-dependent apoptosis in human leukemia HL-60 cells by paclitaxel. Clin Chem Acta 357(1) : 65, 2005 https://doi.org/10.1016/j.cccn.2005.02.003
  19. Park SJ, Wu CW, John D et al : Taxol Induces Caspase-10-dependent Apoptosis. J Bio Chem 279(49) : 51057, 2004 https://doi.org/10.1074/jbc.M406543200
  20. Laupacis A, Keown PA, Ulan RA : Cyclosporin A : a powerful immunosuppessant. Can med Assoc J 126 : 1041, 1986
  21. Satoshi M, Shigeo K : Mechanisms of action of cyclosporine. Immunopharm 47 : 119, 2000 https://doi.org/10.1016/S0162-3109(00)00192-2
  22. Braida M, Knop J : Effect of cyclosporin A on the T-effector and T-suppressor cell response in contact sensitivity. Immun 59 : 503, 1986
  23. Mongini C, Waldner C, Lopes EC et al : Induction of apoptosis in murine lymphoma cells by cyclosporin A. Int J Mol Med 7(4) : 431, 2001
  24. Healy E, Dempsey M, Lally C et al : Apoptosis and necrosis : mechanisms of cell death induced by cyclosporine A in a renal proximal tubular cell line. Kidney Int 54(6) : 1955, 1998 https://doi.org/10.1046/j.1523-1755.1998.00202.x
  25. Justo P, Lorz C, Sanz A et al : Intracellular mechanisms cyclosporin A-induced tubular cell apoptosis. J Am Soc Nephrol 14(12) : 3072, 2003 https://doi.org/10.1097/01.ASN.0000099383.57934.0E
  26. Zupanska A, Dziembowska M, Ellert MA et al : Cyclosporine A induces growth arrest or programmed cell death of human glioma cells. Neuro chem Int 47(6) : 430, 2005 https://doi.org/10.1016/j.neuint.2005.05.010
  27. Lim HW, Kim KW : Anti-cancer Effect of Cyclosporin A on oral squamous cell carcinoma cell line. J Kor Oral Maxillofac Surg 30(6) : 474, 2004
  28. Nomura T, Yamamoto H, Mimata H et al : Enhancement by cyclosporin A of taxol-indeced apoptosis of human urinary bladder cancer cells. Urol Res 30(2) : 102, 2002 https://doi.org/10.1007/s00240-002-0239-4
  29. Ross HJ, Canada AL, Slater LM : Cyclosporin A enhances paclitaxel toxicity against leukemia and respiratory epithelial cancers. Clin Cancer Res 3 : 57, 1997
  30. Sood AK, Sorosky JI, Squatrito RC et al : Cyclosporin A reverse chemoresistance in patients with gynecologic malignancies. Neoplasia 1 : 118, 1999 https://doi.org/10.1038/sj.neo.7900019
  31. Sindermann JR, Skaletz-Rorowski A, Bartels A et al : Paclitaxel and cyclosporine A show supra-additive antiproliferative effects on smooth muscle cells by activation of protein kinases C. Basic Res Cardiol 97(2) : 125, 2002 https://doi.org/10.1007/s003950200002
  32. Meerum-Terwogt JM, Malingre MM, Beijnen JH et al : Coadministration of oral cyclosporin A enables oral therapy with paclitaxel. Clin Cancer Res 5 : 3379, 1999
  33. Kimura Y, Aoki J, Kohno M et al : P-glycoprotein inhibition by the multidrug resistance-reversing agent MS-209 enhances bioavailability and antitumor efficacy of orally administered paclitaxel. Cancer Chemother Pharmacol 49(4) : 322, 2002 https://doi.org/10.1007/s00280-001-0419-x
  34. Mirte MM, Dick JR, Jos H et al : Coadministration of Cyclosporine strongly enhances the oral bioavailability of docetaxel. J Clin Oncology 19(4) : 1160, 2001 https://doi.org/10.1200/JCO.2001.19.4.1160
  35. Koshkina NV, Golunski E, Roberts LE et al : Cyclosporin A aerosol improves the anticancer effect of paclitaxel aerosol in mice. J Aerosol Med 17(1) : 7, 2004 https://doi.org/10.1089/089426804322994415
  36. Kaufmann SH, Earnshaw WC : Induction of apoptosis by cancer chemotherapy. Exp Cell Res 256(1) : 42, 2000 https://doi.org/10.1006/excr.2000.4838
  37. Hengartner MO : The biochemistry of apoptosis. Nature 40(6805) : 770, 2000
  38. Meier P, Finch A, Evan G : Apoptosis in development. Nature 407(6805) : 796, 2000 https://doi.org/10.1038/35037734
  39. Haldar S, Basu A, Croce CM : Bcl-2 is the guardian of microtubule integrity. Cancer Res 57(2) : 229, 1997
  40. Ibrado AM, Liu L, Bhalla K : Bcl-xL overexpression inhibits progression of molecular events leading to paclitaxel-induced apoptosis of human acute myeloid leukemia HL-60 cells. Cancer Res 57 : 1109, 1997
  41. Fana V, Sara V, Patrizia B et al : Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis. Exp cell Res 241 : 96, 1998 https://doi.org/10.1006/excr.1998.4018
  42. Lin HL, Lui WY, Liu TY et al : Reversal of Taxol resistance in hepatoma by cyclosporin A : involvement of the Pl-3 Kinase-AKT 1 pathway. Brit J Can 88 : 973, 2003 https://doi.org/10.1038/sj.bjc.6600788
  43. Susin SA, Lorenza HK, Zamzami N et al : Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397 : 441, 1999 https://doi.org/10.1038/17135
  44. Martin Crompton : The mitochondrial permeability transition pore and its role in cell death. Biochem 341 : 233, 1999 https://doi.org/10.1042/0264-6021:3410233
  45. Crompton MB : Bid and the permeabilization of mitochondrial outer membrane in apoptosis. Curr Opin Cell Biol 12(4) : 414, 2000 https://doi.org/10.1016/S0955-0674(00)00110-1
  46. Li H, Zhu H, Xu C et al : Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94(4) : 491, 1998 https://doi.org/10.1016/S0092-8674(00)81590-1
  47. Wieder T, Essmann F, Prokop A et al : Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3. Blood 97(5) : 1378, 2001 https://doi.org/10.1182/blood.V97.5.1378
  48. Reed JC : Prosmise and problem of Bcl-2 antisene therapy. J Natl Cancer Inst 89 : 988, 1997 https://doi.org/10.1093/jnci/89.14.988
  49. Amundson SA : An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Reserch 60 : 6101, 2000
  50. Hertz C, Vitte PA, Bombrun A et al : Bax channel inhibitors prevent mitochondrial-mediated apoptosis and protect neurons in a model of global brain ischemia. J Biol Chem 280(52) : 42960, 2005 https://doi.org/10.1074/jbc.M505843200
  51. Hwang CS, Choi CO, Kim IS : Detection of Bcl2 & Bax Expression in the Head and Neck Cancers. J Kor Can Asso 27(4) : 570, 1995
  52. Amos LA, Lowe J : How Taxol stabilises microtubule structure. Chem. Biol 6 : 65, 1999 https://doi.org/10.1016/S1074-5521(99)89002-4
  53. Kumar N : Taxol-induced polymerization of purified tubulin. J Biol Chem 256 : 10435, 1981
  54. Linus TC, Eva L, Kenton RC et al : Alteration of lymphocyte microtuble assembly, cyctotoxicity, and activation by the anticancer drug taxol. Cancer Res 41 : 286, 1994
  55. Thomas S, Linda S, Stanley K et al : BAX enhance paclitaxel-induced apoptosis through a p53-independent pathway Proc Natl Acad Sci USA 93(24) : 14094, 1996
  56. Sonnichsen DS, Liu Q, Scheutz EG et al : Variability in human cytochrome P450 paclitaxel metabolism. J Pharm Exp Ther 275 : 566, 1995