The Journal of Internal Korean Medicine (대한한방내과학회지)

The Society of Internal Korean Medicine (대한한방내과학회)
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Anticancer and Related Immunomodulatory Effects of Kwibi-tang on Non-small Cell Lung Carcinoma, NCI-H520, Xenograft Mice

귀비탕(歸脾湯)이 비소세포 폐암세포(NCI-H520) 이식 마우스에서 항암 및 면역 활성에 미치는 영향

  • Son, Ji-Young (Dept. of Internal Medicine, College of Oriental Medicine, Daegu Haany University) ;
  • Choi, Hae-Yun (Dept. of Internal Medicine, College of Oriental Medicine, Daegu Haany University) ;
  • Kim, Jong-Dae (Dept. of Internal Medicine, College of Oriental Medicine, Daegu Haany University)
  • 손지영 (대구한의대학교 한의과대학 내과학교실) ;
  • 최해윤 (대구한의대학교 한의과대학 내과학교실) ;
  • 김종대 (대구한의대학교 한의과대학 내과학교실)
  • Published : 2012.12.30
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Abstract

Objectives : This study was to observe anticancer and related immunomodulatory effects of Kwibi-tang extracts (KBTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of KBTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, each of 8 mice per group were used in the present study. Changes in body weight, tumor volume and weight, lymphatic organs (spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes NK cell activity and peritoneal macrophage activities, splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. The results were compared with a potent cytotoxic anticancer agent, 5-FU (5-Fluorouracil) 30 mg/kg, intraperitoneal treatment (3-day intervals for 42 days, the optimal effective treatment regimes already confirmed). Results & Conclusions : This study suggest that over 50 mg/kg of KBTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory effects. Although relatively lower anticancer effects were observed in KBTe 200 mg/kg treated mice as compared with 5-FU 30 mg/kg treated mice, no meaningful favorable immunomodulatory effects were observed after 5-FU treatment in the present study.

Keywords

References

  1. 통계청. 보건/사망원인시군구/사망원인(50항목) /성/사망자수, 사망률, 연령표준화 사망률(2005-) [internet]. 국가통계포털. [cited 2012 Nov 01]. Available at: http://kosis.kr.
  2. 박재갑, 박찬일, 김노경. 종양학. 서울: 일조각; 2003, p. 304.
  3. 김선영, 김근화. 폐암 항암화학요법의 최신지견. 결핵 및 호흡기질환 2000;49(5):533-45.
  4. 오인재. 비소세포 폐암 세포주에 대한 항암 약제와 방사선 병합치료 방법의 개발. 학위논문(박사). 전남대학교 대학원; 2008.
  5. Curran W, Scott C, Langer C, Komaki R, Lee JS, Hauser S. Phase III comparison of sequential vs comcurrent chemoradiation for patients (Pts) with unresected stage III non-small cell lung cancer (NSCLC): Initial report of radiation teraphy oncology group (RTPG) 9410. Proc Am Sco Clin Oncol 2000;19:484a.
  6. 박철규, 김규식, 오인재, Tseden-Ish Manaljav, 최유덕, 권용수, 등. 재발성 비소세포 폐암에서 Pemetrexed 치료 효과와 Thymidylate Synthase 발현의 관계. 결핵 및 호흡기질환 2009;67:191-8.
  7. 조광현. 새로운 항암제 의한 피부부작용. 대한피부과학회지 2010;48(4):257-65.
  8. 유승후, 유화승, 조종관, 이연월. 항암단을 투여한 재발성 편평상피폐암 환자에 대한 7년간의 추적조사. 대한한방내과학회지 2007;28(2):385-90.
  9. 박봉기, 유화승, 이연월, 한성수, 조정효, 손창규, 등. 수레바퀴 암치료를 시행한 폐암환자에 대한 후향적코호트 분석. 대한한방내과학회지 2008; spr(1):45-56.
  10. 손지영, 최규호, 유효정, 김희준, 구자환, 박미연, 등. 호흡곤란을 주소로 한 폐암환자의 한방치료 증례보고. 대한한방내과학회지 2009;30(1):233-40.
  11. 김경순, 정태영, 유화승, 이연월, 조종관. 항암플러스 투여로 호전된 진행성 비소세포성 폐암 연속환자 증례. 대한한방내과학회지 2009;30(4) :893-900.
  12. 이승언, 홍재의, 이시형, 신조영, 노승석. 폐암 세포주 H460에 대한 補中益氣湯의 세포괴사효 과 및 기전연구. 대한한방내과학회지 2004;25(4) :274-88.
  13. 강윤경, 박동일, 이준혁, 최영현. 潤肺散에 의한 폐암 세포 증식억제기전에 관한 연구. 동의생리병리학회지 2002;164:745-55.
  14. 김진영, 김현중, 정광식, 박철, 감철우, 박동일, 등. A539 및 NCI-H460 인체 폐암 세포의 증식 및 세포사멸 유도에 미치는 加味蔘芪補肺湯의 영향 대한한방내과학회지 2008;29(1):130-48.
  15. 嚴用和. 濟生方. 北京: 人民衛生出版社; 1980, p. 117.
  16. 김형철, 정대규. 歸脾湯, 加味溫膽湯 및 歸脾溫膽湯의 抗 Stress 效能比較硏究. 동의신경정신과학회지 1993;4:99-119.
  17. 박선동, 박현준, 주왕석. 歸脾湯 및 그 구성약물군이 항산화효과에 미치는 영향. 대한본초학회지 2001;16:11-27.
  18. 임동욱, 유동열, 김동희. 加味歸碑湯 免疫調節作用에 미치는 影響. 대한한방부인과학회지 1999;12:253-80.
  19. Busta I, Xie HS, Kim MS. The use of Gui-Pi-Tang in small animals with immune -mediated blood disorders. J Vet Clin 2009; 26:181-4.
  20. 김성호, 이송은, 오헌, 양정아, 정치영, 장종식, 등. 생쥐에서 歸脾湯 및 구성단미의 방사선 방호효과. 한국식품영양과학회지 1999;28:698-704.
  21. Deveau AM, Costa NE, Joshi E, Macdonald L. Synthesis of diketopiperazine-based carboline homodimers and in vitro growth inhibition of human carcinomas. Bioorg Med Chem Lett 2008;18:3522-5. https://doi.org/10.1016/j.bmcl.2008.05.022
  22. Shimizu Y, Kinoshita I, Kikuchi J, Yamazaki K, Nishimura M, Birrer MJ, et al. Growth inhibition of non-small cell lung cancer cells by AP-1 blockade using a cJun dominantnegative mutant. Br J Cancer 2008;98:915-22. https://doi.org/10.1038/sj.bjc.6604267
  23. Cooks T, Schmidt M, Bittan H, Lazarov E, Arazi L, Kelson I, et al. Local control of lung derived tumors by diffusing alpha-emitting atoms released from intratumoral wires loaded with radium-224. Int J Radiat Oncol Biol Phys 2009;74:966-73. https://doi.org/10.1016/j.ijrobp.2009.02.063
  24. Institute of Laboratory Animal Resourcis (Commission on Life Science, National Research Council, USA), Guide for the care and use of laboratory animals. 7. Washington, D.C.: National Academic press; 1996, p. 1-118.
  25. Itoh H, Ito H, Amano H, Noda H. Inhibitory action of a (1-->6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill ("himematsutake") on Meth A fibrosarcomabearing mice and its antitumor mechanism. Jpn J Pharmacol 1994;66:265-71. https://doi.org/10.1254/jjp.66.265
  26. Nishimura G, Yanoma S, Mizuno H, Kawakami, Tsukuda M. An antioxidant, probucol, induces anti-angiogenesis and apoptosis in athymic nude mouse xenografted human head and neck squamous carcinoma cells. Jpn J Cancer Res 1999;90(11):1224-30. https://doi.org/10.1111/j.1349-7006.1999.tb00700.x
  27. Liu L, Jiang Z, Teng GJ, Song JZ, Zhang DS, Guo QM, et al. Clinical and experimental study on regional administration of phosphorus 32 glass microspheres in treating hepatic carcinoma. World J Gastroenterol 1999;5:492-505. https://doi.org/10.3748/wjg.v5.i6.492
  28. Raffaghello L, Marimpietri D, Pagnan G, Pastorino F, Cosimo E, Brignole C, et al. Anti-GD2 monoclonal antibody immunotherapy: a promising strategy in the prevention of neuroblastoma relapse. Cancer Lett 2003;197:205-9. https://doi.org/10.1016/S0304-3835(03)00100-9
  29. Clark BD, Bedrosian I, Schindler R, Cominelli F, Cannon JG, Shaw AR, et al. Detection of interleukin 1 alpha and 1 beta in rabbit tissues during endotoxemia using sensitive radioimmunoassays. J Appl Physiol 1991;71 :2412-8. https://doi.org/10.1152/jappl.1991.71.6.2412
  30. Hotchkiss RS, Osborne DF, Lappas GD, Karl IE. Calcium antagonists decrease plasma and tissue concentrations of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-1 alpha in a mouse model of endotoxin. Shock 1995;3:337-42.
  31. 김명훈, 박희선, 강현모, 장필순, 이연선, 안진영, 등. 제 IV병기 비소세포 폐암의 예후인자. 결핵 및 호흡기질환 2002;53:380.
  32. 김동희, 김성훈. 항암제 및 방사선 부작용에 대한 한방요법. 대한동의병리학회지 1994;9:239-64.
  33. 方葯中, 鄧鐵淺, 李克光, 陳可冀, 金壽山, 黃星垣, 등. 실용중의내과학. 상해: 상해과학기술 출판사; 1986, p. 621-36.
  34. 문구, 정병학, 김병주. 암동서의결합치료(I). 익산: 원광대학교출판국; 1999, p. 253-303, 383-460.
  35. 국윤범, 김상찬, 박선동, 박성규, 서부일, 서영 배, 등. 方劑學. 서울: 영림사; 2008, p. 290-2.
  36. Hanada M, Noguchi T, Yamaoka T. Amrubicin, a novel 9-aminoanthracycline, enhances the antitumor activity of chemotherapeutic agents against human cancer cells in vitro and in vivo. Cancer Sci 2007;98:447-54. https://doi.org/10.1111/j.1349-7006.2007.00404.x
  37. Okabe T, Okamoto I, Tsukioka S, Uchida J, Hatashita E, Yamada Y, et al. Addition of S-1 to the epidermal growth factor receptor inhibitor gefitinib overcomes gefitinib resistance in non-small cell lung cancer cell lines with MET amplification. Clin Cancer Res 2009;15 :907-13. https://doi.org/10.1158/1078-0432.CCR-08-2251
  38. Natsume T, Watanabe J, Horiuchi T, Kobayashi M. Combination effect of TZT-1027 (Soblidotin) with other anticancer drugs. Anticancer Res 2006;26:1145-51.
  39. Foster PA. Steroid metabolism in breast cancer. Minerva Endocrinol 2008;33:27-37.
  40. Kim YC, Kwon YS, Oh IJ, Kim KS, Kim SY, et al. National survey of lung cancer in Korea, 2005. J Lung Cancer 2007;6:67-73. https://doi.org/10.6058/jlc.2007.6.2.67
  41. Kondo H, Kanzawa F, Saito S, Saijo N. In vitro and in vivo effects of cisplatin and etoposide in combination on small cell lung cancer cell lines. Jpn J Cancer Res 1994;85(10) :1050-6. https://doi.org/10.1111/j.1349-7006.1994.tb02905.x
  42. Sogn JA. Tumor immunology: the glass is half full. Immunity 1998;9:757-63. https://doi.org/10.1016/S1074-7613(00)80641-X
  43. Finke J, Ferrone S, Frey A, Mufson A, Ochoa A. Where have all the T cells gone? Mechanisms of immune evasion by tumors. Immunol Today 1999;20:158-60. https://doi.org/10.1016/S0167-5699(98)01435-2
  44. Pawelec G, Heinzel S, Kiessling R, Muller L, Ouyang Q, Zeuthen J. Escape mechanisms in tumor immunity: a year 2000 update. Crit Rev Oncog 2000;97-133.
  45. Ha ES, Hwang SH, Shin KS, Yu KW, Lee KH, Choi JS, et al. Anti-metastatic activity of glycoprotein fractionated from Acanthpanax senticosus, involvement of NK-cell and macrophage activation. Arch Pharm Res 2004;27:217-24. https://doi.org/10.1007/BF02980109
  46. Yu GM, Hwang IG. In vitro effect of Yuza (Citrus junos SIEB ex TANAKA) extracts on proliferation of human prostate cancer cells and antioxidant activity. Korean J Food Sci Technol 2004;36:339-44.
  47. Sharkey FE, Fogh J. Considerations in the use of nude mice for cancer research. Cancer Metastasis Rev 1984;3:341-60. https://doi.org/10.1007/BF00051459
  48. Kennedy JD, Pierce CW, Lake JP. Extrathymic T cell maturation. Phenotypic analysis of T cell subsets in nude mice as a function of age. J Immunol 1992;148:1620-9.
  49. Cheng WH, Holmstrom A, Li X, Wu R., Zeng H, Xiao Z. Effect of dietary selenium and cancer cell xenograft on peripheral T and B lymphocytes in adult nude mice. Biol Trace Elem Res 2012;146(2):230-5. https://doi.org/10.1007/s12011-011-9235-2
  50. Ferguson T. Prevention and delay of spontaneous mammary and pituitary tumors by long- and short-term ingestion of 5-fluorouracil in Wistar -Furth rats. Oncology 1980;37:353-6. https://doi.org/10.1159/000225468
  51. Habs M, Schmähl D, Lin PZ. Carcinogenic activity in rats of combined treatment with cyclophosphamide, methotrexate and 5-fluorouracil. Int J Cancer 1981;28:91-6. https://doi.org/10.1002/ijc.2910280116