DOI QR코드

DOI QR Code

인삼양영탕(人蔘養榮湯)이 비소세포 폐암세포(NCI-H520) 이식 마우스에서 항암 및 면역 활성에 미치는 영향

Anticancer and Related Immunomodulatory Effects of Insamyangyoung-tang on Non-small Cell Lung Carcinoma, NCI-H520, Xenograft Mice

  • 송광규 (대구한의대학교 한의과대학 내과학교실) ;
  • 곽민아 (대구한의대학교 한의과대학 내과학교실) ;
  • 김종대 (대구한의대학교 한의과대학 내과학교실)
  • Song, Kwang-Kyu (Department of Internal Medicine, College of Korean Medicine, Daegu Haany University) ;
  • Kwak, Min-A (Department of Internal Medicine, College of Korean Medicine, Daegu Haany University) ;
  • Kim, Jong-Dae (Department of Internal Medicine, College of Korean Medicine, Daegu Haany University)
  • 투고 : 2013.05.20
  • 심사 : 2013.06.07
  • 발행 : 2013.06.30

초록

Objectives : The object of this study was to observe anticancer and related immunomodulatory effects of Insamyangyoung-tang extracts (ISYYTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of ISYYTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, which are intact control, tumor bearing control, 5-fluorouracil (FU) 30 mg/kg, ISYYTe 50 mg/kg, ISYYTe 100 mg/kg, ISYYTe 200 mg/kg, each of 8 mice per group were used in the present study. Changes on the body weight, tumor volume and weight, lymphatic organ (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. Results : As results of ISYYTe 50, 100 and 200 mg/kg treatment, decreases in the tumor volumes and weights were detected. At histopathological observations, decreases of tumor cell volumes in tumor masses were dose-dependently decreased mediated by increases of apoptosis among tumor cells by treatment of all three different dosages of ISYYTe. As results of tumor cell inoculation, marked decreases of spleen and popliteal lymph node weights, serum IFN-${\gamma}$, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents and splenocytes were observed with histopathological atrophic changes of spleen and popliteal lymph nodes. Conclusions : Over 50 mg/kg of ISYYTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory effects. Although relatively lower anticancer effects were observed in ISYYTe 200 mg/kg treated mice as compared with 5-FU 30 mg/kg treated mice, there are no meaningful favorable immunomodulatory effects were observed after 5-FU treatment in the present study.

키워드

참고문헌

  1. Korea National Statistic Office. 2007 annual report on the cause of death statistics. 2008. Available from: URL:http://nso.go.kr
  2. Kim YC, Kwon YS, Oh IJ, Kim KS, Kim SY, Ryu JS. 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
  3. Yang CH, Tsai CM, Wang LS, Lee YC, Chang CJ, Lui LT, Yen SH, Hsu C, Cheng AL, Liu MY, Chiang SC, Chen YM, Luh KT, Huang MH, Yang PC, Perng RP. Gemcitabine and cisplatinina multimodality treatment for locally advanced non-small cell lung cancer. Br J Cancer. 2002;86:190-5. https://doi.org/10.1038/sj.bjc.6600044
  4. Scarpati MD, Vicidomini G, Santini M. Gemcitabine and small cell lung cancer. Lung Cancer. 2001;34:313-4. https://doi.org/10.1016/S0169-5002(01)00237-9
  5. Worden FP, Kalemkerian GP. Therapeutic advances in small cell lung cancer. Expert Opin Investig Drugs. 2000;9:565-79. https://doi.org/10.1517/13543784.9.3.565
  6. Massarelli E, Herbst RS. Use of novel secondline targeted therapies in non-small cell lung cancer. Semin Oncol. 2006;33:9-16. https://doi.org/10.1053/S0093-7754(06)00407-6
  7. Steinke K. Lung tumors. Recent Results Cancer Res. 2006;167:107-22. https://doi.org/10.1007/3-540-28137-1_8
  8. Lee HB, Kim HJ, Chong MS, Cho HE, Choi YH, Lim KS, Lee KN. Physiological activity of extracts from mixed culture of medical herbs and mycelia of Tricholoma matsutake and Cordyceps militaris by fermentation. Kor J Herbology. 2008;23:1-8.
  9. Ham YA, Choi HJ, Kim SH, Chung MJ, Ham SS. Antimutagenic and antitumor effects of Adenophora triphylla Extracts. J Korean Soc Food Sci Nutr. 2009;38:25-31. https://doi.org/10.3746/jkfn.2009.38.1.025
  10. Yu MH, Im HG, Lee HJ, Ji YJ, Lee IS. Components and their antioxidative activities of methanol extracts from sarcocarp and seed of Zizyphus jujuba var. inermis Rehder. Korean J Food Sci Technol. 2006;38:128-34.
  11. Eun JS, Kim DK, Choi H, Oh CH. Effect of Insamyangyoung-tang on the Specific Immune Response in BALB/c Mice. Korean J Oriental Physiology & Pathology. 2002;16:729-33.
  12. Ha JY, Jo SY. Effect of Insamyangyoungtang on the Anticancer and Immunomodulating effect. Korean J Oriental Physiology & Pathology. 1998;12:60-71.
  13. Institute of Laboratory Animal Resources (Commission on Life Science, National Research Council, USA). Guide for the care and use of laboratory animals. 7th ed. Washington:National Academic press. 1996:1-118.
  14. Itoh H, Ito H, Amano H, Noda H. Inhibitory action of a (1-->6)-beta-D- glucan-protei n complex (FIII-2-b) isolated from Agaricu s blazei Murill ("himematsutake") on Meth A fibrosarcoma-bearing mice and its antitumor m echanism. Jpn J Pharmacol. 1994;66:265-71. https://doi.org/10.1254/jjp.66.265
  15. Nishimura G, Yanoma S, Mizuno H, Kawakami K, Tsukuda M. An antioxidant, probucol, induces anti-angiogenesis and apoptosis in ath ymic nude mouse xenografted human head and neck squamous carcinoma cells. Jpn J Cancer Res. 1999;90:1224-30. https://doi.org/10.1111/j.1349-7006.1999.tb00700.x
  16. Liu L, Jiang Z, Teng GJ, Song JZ, Zhang DS, Guo QM, Fang W, He SC, Guo JH. 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
  17. Raffaghello L, Marimpietri D, Pagnan G, Pastorino F, Cosimo E, Brignole C, Ponzoni M, Montaldo PG. 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
  18. Clark BD, Bedrosian I, Schindler R, Cominelli F, Cannon JG, Shaw AR, Dinarello CA. Detection of interleukin 1 alpha and 1 beta in rabbit tissues during endotoxemia using sensitive radioimmunoassays. J Appl Physiol. 1991;71:2412-8.
  19. 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.
  20. Society for Pathology of Korea. Chapter of Daegu Kyungbuk. Pathology Digest. Seoul: Jeongmoonsa, 2008:191-217.
  21. Oh IJ. Development of Combination Treatment of Anticancer drug and Radiotherapy in Nonsmall Cell Lung Carcinoma. Doctoral thesis of Chonnam University. 2008.
  22. Korea National Statistical Office. Death rate statistics of Korea, 2005. Seoul, Korea National Statistical Office, 2007.
  23. Scientific Committee of Korean Academy of Tuberculosis and Respiratory Diseases. The national survey of lung cancer in Korea. Tuberc Respir Dis. 1999;46:455-65. https://doi.org/10.4046/trd.1999.46.4.455
  24. Peng HR. Dictionary of formulas of traditional chinese medicine(first book). Beijing:People's Health Publishing House. 1995;467.
  25. Kuk YB, Kim SC, Park SD, Park SK, Seo BI, Seo YB, etc. Oriental Medicine Prescription. Seoul:Younglimsa, 2008:294.
  26. Hur J. Translated with Korean Enlarged Dongeuibogam. Seoul:Namsandang. 1992:671.
  27. 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
  28. Okabe T, Okamoto I, Tsukioka S, Uchida J, Hatashita E, Yamada Y, Yoshida T, Nishio K, Fukuoka M, Janne PA, Nakagawa K. 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
  29. Natsume T, Watanabe J, Horiuchi T, Kobayashi M. Combination effect of TZT-1027 (Soblidotin) with other anticancer drugs. Anticancer Res. 2006;26:1145-51.
  30. Samira S, Ferrand C, Peled A, Nagler A, Tovbin Y, Ben-Hur H, Taylor N, Globerson A, Lapidot T. Tumor necrosis factor promotes human Tcell development in nonobese diabetic/severe combined immunodeficient mice. Stem Cells. 2004;22:1085-100. https://doi.org/10.1634/stemcells.22-6-1085
  31. Isaacs A. Lymphokines and Cytokines. In: Tizard IR. Immunology an introduction. 4th ed. Philadelphia:Saunders. 1995:155-69.
  32. Unanue ER. The Mononuclear Phagocytic System. In: Tizard IR. Immunology an introduction. 4th ed. Philadelphia:Saunders, 1995:61-74.
  33. Sogn JA. Tumor immunology: the glass is half full. Immunity. 1998;9:757-63. https://doi.org/10.1016/S1074-7613(00)80641-X
  34. Finke J, Ferrone S, Frey A, Mufson A, Ochoa A. Where have all the T cells gone? Mecha nisms of immune evasion by tumors. Immunol Today. 1999;20:158-60. https://doi.org/10.1016/S0167-5699(98)01435-2
  35. 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;11:97-133.
  36. Ha ES, Hwang SH, Shin KS, Yu KW, Lee KH, Choi JS, Park WM, Yoon TJ. Anti-metastatic activity of glycoprotein fractionated from Acanthpanax senticosus, involvement of NKcell and macrophage activation. Arch Pharm Res. 2004;27:217-24. https://doi.org/10.1007/BF02980109
  37. 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.
  38. Schimmel KJ, Richel DJ, van den Brink RB, Guchelaar HJ. Cardiotoxicity of cytotoxic drugs. Cancer Treat Rev. 2004;30:181-91. https://doi.org/10.1016/j.ctrv.2003.07.003
  39. Dalzell JR, Samuel LM. The spectrum of 5-fluorouracil cardiotoxicity. Anticancer Drugs. 2009;20:79-80. https://doi.org/10.1097/CAD.0b013e3283165f27

피인용 문헌

  1. A Study on Roman Nomenclature of Prescriptions in Herbal Formula Science vol.21, pp.2, 2013, https://doi.org/10.14374/HFS.2013.21.2.013