Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지

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

인삼양영탕(人蔘養榮湯)이 비소세포 폐암세포 이식 마우스에서 항암, 면역활성 및 악액질 억제에 미치는 영향

  • Song, Kwang Kyu (Haein Couple Korean Clinic) ;
  • Park, Mee Yeon (Division of Intenal Medicine, College of Korean Medicine, Daegu Haany University) ;
  • Choi, Hae Yun (Division of Intenal Medicine, College of Korean Medicine, Daegu Haany University) ;
  • Kim, Jong Dae (Division of Intenal Medicine, College of Korean Medicine, Daegu Haany University)
  • 송광규 (해인부부한의원) ;
  • 박미연 (대구한의대학교 한의학과 내과학교실) ;
  • 최해윤 (대구한의대학교 한의학과 내과학교실) ;
  • 김종대 (대구한의대학교 한의학과 내과학교실)
  • Received : 2012.10.26
  • Accepted : 2013.01.08
  • Published : 2013.02.25
Download PDF
⟨ Previous Next ⟩

Abstract

The object of this study was to observe anticancer and related immunomodulatory and anticachexic effects of Insamyangyoung-tang aqueous extracts (ISYYTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Changes on the tumor volume and weights, lymphatic organ(spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes and peritoneal macrophage activities (NK cell activity), splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents, splenic T-lymphocyte subsets (CD3+, CD4+ and CD8+) and TNF-${\alpha}+$ cells were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. In addition, changes on the body weights, epididymal fat weights and serum IL-6 levels were also detected with the thicknesses of deposited cervical brown adipose tissue and their mean diameters to monitor the tumor-related anticachexic effects. The results obtained in this study suggest that over 50 mg/kg of ISYYTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory and anticachexic effects. However, detail mechanism studies should be conducted in future with the screening of the biological active compounds in this herb.

Keywords

References

  1. Korea National Statistic Office. 2007 annualreporton the cause of death statistics. 2008. (http://nso.go.kr)
  2. Kim, Y.C., Kwon, Y.S., Oh, I.J., Kim, K.S., Kim, S.Y., Ryu, J.S. National survey of lung cancer in Korea, 2005. J. Lung Cancer, 6: 67-73, 2007. https://doi.org/10.6058/jlc.2007.6.2.67
  3. 한용철. 임상호흡기학. 서울. 일조각. p 137, 1995.
  4. Nelson, K.A., Walsh, D., Sheehan, F.A. The cancer anorexiacachexia syndrome. J of Clinical Oncology 12(1):213-225, 1994. https://doi.org/10.1200/JCO.1994.12.1.213
  5. 김은경, 양영희, 최스미. 입원한 암환자의 영양상태연구. 대한간호학회지 29(2):271-280, 1999.
  6. 翁家武, 陳培丰. 癌症惡病質的中醫藥治療研究进展. 浙江中西醫結合雜誌 19(2):123-125, 2009.
  7. Yang, C.H., Tsai, C.M., Wang, L.S., Lee, Y.C., Chang, C.J., Lui, L.T., Yen, S.H., Hsu, C., Cheng, A.L., Liu, M.Y., Chiang, S.C., Chen, Y.M., Luh, K.T., Huang, M.H., Yang, P.C., Perng, R.P. Gemcitabine and cisplatinina multimodality treatment for locally advanced non-small cell lung cancer. Br J Cancer 86: 190-195, 2002. https://doi.org/10.1038/sj.bjc.6600044
  8. Scarpati, M.D., Vicidomini, G., Santini, M. Gemcitabine and small cell lung cancer. Lung Cancer 34: 313-314, 2001. https://doi.org/10.1016/S0169-5002(01)00237-9
  9. Worden, F.P., Kalemkerian, G.P. Therapeutic advances in small cell lung cancer. Expert Opin Investig Drugs 9: 565-579, 2000. https://doi.org/10.1517/13543784.9.3.565
  10. Massarelli, E., Herbst, R.S. Use of novel second-line targeted therapies in non-small cell lung cancer. Semin Oncol 33: 9-16, 2006. https://doi.org/10.1053/S0093-7754(06)00407-6
  11. Steinke, K. Lung tumors. Recent Results Cancer Res, 167: 107-122, 2006. https://doi.org/10.1007/3-540-28137-1_8
  12. Lee, H.B., Kim, H.J., Chong, M.S., Cho, H.E., Choi, Y.H., Lim, K.S., Lee, K.N. Physiological activity of extracts from mixed culture of medical herbs and mycelia of Tricholoma matsutake and Cordyceps militaris by fermentation. Kor J Herbology 23: 1-8, 2008.
  13. Ham, Y.A., Choi, H.J., Kim, S.H., Chung, M.J., Ham, S.S. Antimutagenic and antitumor effects of Adenophora triphylla Extracts. J. Korean Soc Food Sci Nutr 38: 25-31, 2009. https://doi.org/10.3746/jkfn.2009.38.1.025
  14. Yu, M.H., Im, H.G., Lee, H.J., Ji, Y.J., Lee, I.S. Components and their antioxidative activities of methanol extracts from sarcocarp and seed of Zizyphus jujuba var. inermis Rehder. Korean J. Food Sci Technol 38: 128-134, 2006.
  15. 은재순, 김대근, 최훈, 오찬호. 人蔘養榮湯이 생쥐의 특이적 면역반응에 미치는 영향. 동의병리학회지 16: 729-733, 2002.
  16. 하지용, 조성연. 人蔘養榮湯이 항암 및 면역조절작용에 미치는 영향. 동의병리학회지 12: 60-71, 1998.
  17. 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. pp 1-118, 1996.
  18. Itoh, H., Ito, H., Amano, H., Noda, H. Inhibitory action of a (1-->6)-beta-D-glucan-protein complex (FIII-2-b) isolated from Agaricus blazei Murill ("himematsutake") on Meth A fibrosarcoma-bearing mice and its antitumor mechanism. Jpn J Pharmacol 66: 265-271, 1994. https://doi.org/10.1254/jjp.66.265
  19. Nishimura, G., Yanoma, S., Mizuno, H., Kawakami, K., Tsukuda, M. An antioxidant, probucol, induces antiangiogenesis and apoptosis in athymic nude mouse xenografted human head and neck squamous carcinoma cells. Jpn J Cancer Res 90: 1224-1230, 1999. https://doi.org/10.1111/j.1349-7006.1999.tb00700.x
  20. Liu, L., Jiang, Z., Teng, G.J., Song, J.Z., Zhang, D.S., Guo, Q.M., Fang, W., He, S.C., Guo, J.H. Clinical and experimental study on regional administration of phosphorus 32 glass microspheres in treating hepatic carcinoma. World J Gastroenterol 5: 492-505, 1999. https://doi.org/10.3748/wjg.v5.i6.492
  21. Iizuka, N., Miyamoto, K., Hazama, S., Yoshino, S., Yoshimura, K., Okita, K., Fukumoto, T., Yamamoto, S., Tangoku, A., Oka, M. Anticachectic effects of Coptidis rhizoma, an anti inflammatory herb, on esophageal cancer cells that produce interleukin 6. Cancer Lett 158: 35-41, 2000. https://doi.org/10.1016/S0304-3835(00)00496-1
  22. Clark, B.D., Bedrosian, I., Schindler, R., Cominelli, F., Cannon, J.G., Shaw, A.R., Dinarello, C.A. Detection of interleukin 1 alpha and 1 beta in rabbit tissues during endotoxemia using sensitive radioimmunoassays. J Appl Physiol 71: 2412-2418, 1991. https://doi.org/10.1152/jappl.1991.71.6.2412
  23. Hotchkiss, R.S., Osborne, D.F., Lappas, G.D., Karl, I.E. 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 3: 337-342, 1995.
  24. Raffaghello, L., Marimpietri, D., Pagnan, G., Pastorino, F., Cosimo, E., Brignole, C., Ponzoni, M., Montaldo, P.G. Anti GD2 monoclonal antibody immunotherapy: a promising strategy in the prevention of neuroblastoma relapse. Cancer Lett 197: 205-209, 2003. https://doi.org/10.1016/S0304-3835(03)00100-9
  25. 대한병리학회 대구경북지부학회(강유나 등, 44명). 간추린 병리학. 서울. 정문사. pp 191-217, 2008.
  26. 吳寅在. 비소세포 폐암 세포주에 대한 항암 약제와 방사선 병합치료 방법의 개발. 전남대학교 대학원 박사학위논문. pp 1-32, 2008.
  27. Korea National Stastical Office. Death rate stastistics of Korea, 2005. Seoul, Korea National Stastical Office, 2007.
  28. Scientific Committee of Korean Academy of Tuberculosis and Respiratory Diseases. The national survey of lung cancer in Korea. Tuberc Respir Dis 46: 455-465, 1999. https://doi.org/10.4046/trd.1999.46.4.455
  29. Clark, J.C., Dass, C.R., Choong, P.F.. Development of chondrosarcoma animal models for assessment of adjuvant therapy. ANZ J Surg 79: 327-336, 2009. https://doi.org/10.1111/j.1445-2197.2009.04884.x
  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 T cell development in nonobese diabetic/severe combined immunodeficient mice. Stem Cells 22: 1085-1100, 2004. https://doi.org/10.1634/stemcells.22-6-1085
  31. Grant, M., Ropka, M.E. Alterations in nutrition. in McCorkle R., Grant, M., Frank, Stromborg, M. and Baird(Eds).S.B. Cancer Nursing, a comprehensive textbook. 2nd ed. Philadelphia, london Saunders, 1996.
  32. Kim, Y.O., Han, B. Association of Nutritional Status with Clinical Outcome of Stomach Cancer Patients. J. Korean Soc Food Sci Nutr 29(6):1185-1189, 2000.
  33. Burtis, G., Caviw, J., Martin, S. Applied nutrition and diet therapy. Philadelphia, W.B. saunder Company. pp 484-487, 1988.
  34. Rivadeneria, .DE., Denis, E., Thomas, J.F., Micheael, D.L., John, M.D. Nutritional support of the cancer patients. CA Cancer J Clin 48: 69-80, 1998. https://doi.org/10.3322/canjclin.48.2.69
  35. Shils, M.E., Olson, J.A., Shike, M. Modern nutrition in health and disease. Philadephia, Lea&Feriger. pp 1319-1326, 1994.
  36. McWhirter, J.P., Pennington, C.R. Incidence and recognition of malnutrition in hospital. BMJ 308: 945-948, 1994. https://doi.org/10.1136/bmj.308.6934.945
  37. Kim, E.K., Yang, Y.H., Choi, S.M. Nutritional Status of Cancer Patients upon Admission. J. Korean Nurses Association 29(2):271-280, 1999.
  38. 송광규, 박미연, 최해윤, 김종대. 암성 악액질의 한약치료에 대한 고찰(2000-2009년까지 중의논문을 중심으로). 한국한의학연구원논문집 16(2):181-191, 2010.
  39. 申載鏞. 方藥合編解說. 서울. 成輔社. p 42, 1988.
  40. 鞠潤範, 金相贊, 朴宣東, 朴性奎, 徐富一, 徐榮培, 申舜植, 李尙仁, 李長泉, 李棣熙, 鄭宗佶, 朱榮丞, 崔湖榮. 方劑學. 서울. 永林社. p 294, 2008.
  41. 許俊. 國譯增補 東醫寶鑑. 서울. 南山堂. p 671, 1992.
  42. 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 98: 447-454, 2007. https://doi.org/10.1111/j.1349-7006.2007.00404.x
  43. Okabe, T., Okamoto, I., Tsukioka, S., Uchida, J., Hatashita, E., Yamada, Y., Yoshida, T., Nishio, K., Fukuoka, M., Janne, P.A., 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 15: 907-913, 2009. https://doi.org/10.1158/1078-0432.CCR-08-2251
  44. Natsume, T., Watanabe, J., Horiuchi, T., Kobayashi, M. Combination effect of TZT-1027 (Soblidotin) with other anticancer drugs. Anticancer Res 26: 1145-1151, 2006.
  45. Foster, P.A. Steroid metabolism in breast cancer. Minerva Endocrinol 33: 27-37, 2008.
  46. Isaacs, A. Lymphokines and Cytokines. In: Immunology an introduction (Tizard IR editor). 4th edition. Philadelphia, Saunders pp 155-169, 1995.
  47. Unanue, E.R. The Mononuclear Phagocytic Sytem. In: Immunology an introduction (Tizard IR editor). 4th edition. Philadelphia, Saunders pp 61-74, 1995.
  48. Sogn, J.A. Tumor immunology: the glass is half full. Immunity 9: 757-763, 1998. https://doi.org/10.1016/S1074-7613(00)80641-X
  49. 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 20: 158-160, 1999. https://doi.org/10.1016/S0167-5699(98)01435-2
  50. Pawelec, G., Heinzel, S., Kiessling, R., Muller, L., Ouyang, Q., Zeuthen, J. Escape mechanisms in tumor immunity: a year 2000 update. Crit Rev Oncog 11: 97-133, 2000.
  51. Jaffe, M.L., Arai, H., Nabel, G.J. Mechanisms of tumor induced immunosuppression: evidence for contact dependent T cell suppression by monocytes. Mol Med 2: 692-701, 1996.
  52. Wang, R.F. Immune suppression by tumor specific CD4+ regulatory T cells in cancer. Semin Cancer Biol 16: 73-79, 2006. https://doi.org/10.1016/j.semcancer.2005.07.009
  53. Hsieh, C.L., Chen, D.S., Hwang, L.H. Tumor induced immunosuppression: a barrier to immunotherapy of large tumors by cytokine secreting tumor vaccine. Hum Gene Ther 11: 681-692, 2000. https://doi.org/10.1089/10430340050015581
  54. Riccobon, A., Gunelli. R., Ridolfi, R., De Paola, F., Flamini, E., Fiori, M., Saltutti, C., Petrini, M., Fiammenghi, L., Stefanelli, M., Granato, A.M., Cuzzocrea, D.E., Amadori, D. Immunosuppression in renal cancer: differential expression of signal transduction molecules in tumor infiltrating, near tumor tissue, and peripheral blood lymphocytes. Cancer Invest 22: 871-877, 2004. https://doi.org/10.1081/CNV-200039653
  55. Ha, E.S., Hwang, S.H., Shin, K.S., Yu, K.W., Lee, K.H., Choi, J.S., Park, W.M., Yoon, T.J. Anti metastatic activity of glycoprotein fractionated from Acanthpanax senticosus, involvement of NK cell and macrophage activation. Arch Pharm Res 27: 217-224, 2004. https://doi.org/10.1007/BF02980109
  56. Yu, G.M., Hwang, I.G. 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 36: 339-344, 2004.
  57. Schimmel, K.J., Richel, D.J., van den Brink, R.B., Guchelaar, H.J. Cardiotoxicity of cytotoxic drugs. Cancer Treat Re, 30: 181-191, 2004. https://doi.org/10.1016/j.ctrv.2003.07.003
  58. Dalzell, J.R., Samue,l L.M. The spectrum of 5-fluorouracil cardiotoxicity. Anticancer Drugs 20: 79-80, 2009. https://doi.org/10.1097/CAD.0b013e3283165f27
  59. Strassmann, G., Fong, M., Kenney, J.S., Jacob, C.O. Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest 89: 1681-1684, 1992. https://doi.org/10.1172/JCI115767
  60. Fujita, J., Tsujinaka, T., Yano, M., Ebisui, C., Saito, H., Katsume, A., Akamatsu, K., Ohsugi, Y., Shiozaki, H., Monden, M. Anti interleukin 6 receptor antibody prevents muscle atrophy in colon 26 adenocarcinoma bearing mice with modulation of lysosomal and ATP ubiquitin dependent proteolytic pathways. Int J Cancer 68: 637-643, 1996. https://doi.org/10.1002/(SICI)1097-0215(19961127)68:5<637::AID-IJC14>3.0.CO;2-Z
  61. Kurebayashi, J., Yamamoto, S., Otsuki, T., Sonoo, H. Medroxyprogesterone acetate inhibits interleukin 6 secretion from KPL 4 human breast cancer cells both in vitro and in vivo: a possible mechanism of the anticachectic effect. Br J Cancer 79: 631-636, 1999. https://doi.org/10.1038/sj.bjc.6690099
  62. Oka, M., Yamamoto, K., Takahashi, M., Hakozaki, M., Abe, T., Iizuka, N., Hazama, S., Hirazawa, K., Hayashi, H., Tangoku, A., Hirose, K., Ishihara, T., Suzuki, T. Relationship between serum levels of interleukin 6, various disease parameters and malnutrition in patients with esophageal squamous cell carcinoma. Cancer Res 56: 2776-2780, 1996.
  63. Wang, L.S., Chow, K.C., Wu, C,W. Expression and upregulation of interleukin 6 in oesophageal carcinoma cells by n sodium butyrate. Br J. Cancer 80: 1617-1622, 1999. https://doi.org/10.1038/sj.bjc.6690571