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흰쥐의 종양에 대한 단삼 추출물의 항종양 활성

Antitumor Activity of Salvia miltiorrhiza Herbal Extract in Rat Tumor Model

  • 박현정 (동신대학교 한의과대학 해부학교실) ;
  • 안상건 (조선대학교 치과대학 병리학교실) ;
  • 김정상 (동신대학교 한의과대학 해부학교실)
  • 발행 : 2007.04.30

초록

흰쥐 우측요부에 RK3E-ras cell주입으로 7일 이내에 종양이 발달하는 것을 관찰하고, 단삼 추출물을 제조하여 항종양 효과를 관찰하고자 1주 후부터 2주 동안 육종 부위에 투여 후 종양의 크기와 무게를 측정하고 조직학적인 관찰을 통하여 암세포의 발달과 암전이 유무를 살펴보았다. 암종의 크기는 대조군에 비하여 단삼 추출물을 투여한 실험군에서 현저히 감소(p<0.01)하였으며, 암종의 중량 또한 실험군에서 현저히 감소(p<0.01)하였다. 조직학적 관찰 결과 종양을 둘러싸고 있는 섬유막은 대조군에 비하여 실험군에서 발달 해 있었으며, 암세포의 밀도는 실험군에 비하여 대조군에서 높았다. 간조직을 관찰한 결과 대조군의 간문맥 주변에서 전이된 것으로 보이는 암세포들이 다수 관찰되었다. 이와 같은 결과를 토대로 단삼 추출물이 항종양효과가 있다고 사료된다.

The present study was carried out to investigate the antitumor activity of Salvia miltiorrhiza (SM) herbal extract in rat tumor model. We used a new tumor animal model for the invasion and metastasis of cancer using genetically k-ras-induced rat kidney cells (RK3E-ras). We observed tumor as early as 7 days after the injection of RK3E-ras cells in subcutaneous of Sprague-Dawley rats. All of the rats developed tumor mass at the inoculated site. After 7 days, the experimental groups were divided into two: saline control and injected with SM (200 mg/kg) groups. We investigated tumor's weight, size and hepatic metastasis of each group. Injection of SM herbal extract every other day for 14 days significantly inhibited tumor growth. Histologically, the tumors were undifferentiated carcinoma showing multifactorial necrosis and hemorrhage; also, the tumor invaded into hepatoportal region. Treatment with SM herbal extract caused significant inhibition of tumor cell proliferation. Our data showed that SM herbal extract is effective in controlling the tendency of tumor cell proliferation and metastasis by injection of RK3E-ras cells. These findings provided the potential value of SM as a novel antitumor agent candidate.

키워드

참고문헌

  1. 대한병리학회. 2003. 병리학. 고문사, 서울. p 143
  2. 서울대학교의과대학편. 2001. 종양학. 제 2 진정판. 서울대학교출판부, 서울. p141-88
  3. 김성훈. 1998. 한의학계의 암 연구 동향과 연구 전략에 대한 연구. 대한한의학회지 191: 470-99
  4. Kronenberg F, Mindes J, Jacobson JS. 2005. The future of complementary and alternative medicine for cancer. Cancer Invest 23: 420-426 https://doi.org/10.1081/CNV-67159
  5. Okamura N, Sato M, Yagi A. 1992. An application of HPLC for identification of abietane-type pigments from Salvia miltiorrhiza and their effects on post-hypoxic cardiac contractile force in rats. Planta Med 58: 571-573 https://doi.org/10.1055/s-2006-961556
  6. Sato M, Sato T, Ose Y, Nagase H, Kito H, Sakai Y. 1992. Modulating effect of tanshinones on mutagenic activity of Trp-P.1 and benzo[a]pyrene in Salmonella Typhimurium. Mutat Res 265: 149-154 https://doi.org/10.1016/0027-5107(92)90043-2
  7. Li ZT, Yang BJ, Ma GE. 1991. Chemical studies of Salvia miltiorrhiza. Yao Hsueh Pao 23: 209-213
  8. 성락기, 김성훈, 이권익. 1996. 丹蔘의 抗癌效果와 活性物質 分離에 關한 硏究. 동의병리학회지 10: 76-91
  9. 남우열, 전병훈. 1997. MMC 등의 抗癌化學療法劑로 誘發된 細胞毒性에 미치는 丹蔘의 影響. 동의병리학회지 11: 113-117
  10. 최선미, 최승훈, 안규석. 2000. 丹蔘의 抗癌活性과 apoptosis에 미치는 影響. 동의병리학회지 14: 22-47
  11. Akla B, Monteil J, Sturtz F, Rigaud M. 2003. A new orthotopic model of human breast cancer immunocompetent rats. Anticancer Res 23: 3761-3766
  12. Choy G, O'Connor S, Diehn FE, Costouros N, Alewander HR, Choyke P, Libutti SK. 2003. Comparison of noninvasive fluorescent and bioluminescent small animal optical imaging. Biotechniques 35: 1028-1030
  13. Gould MN. 1995. Rodent models for the study of etiology, prevention and treatment of cancer. Semin Cancer Biol 6: 147-152 https://doi.org/10.1006/scbi.1995.0023
  14. Hutchinson JN, Muller WJ. 2000. Transgenic mouse models of human breast cancer. Oncogene 19: 6130-6137 https://doi.org/10.1038/sj.onc.1203970
  15. Barbacid M. 1987. Ras genes. Annu Rev Biochem 56: 779-827 https://doi.org/10.1146/annurev.bi.56.070187.004023
  16. Caulin C, Nguyen T, Longley MA, Zhou Z, Wang XJ, Roop DR. 2004. Inducible activation of oncogenic K-ras regults in tumor formation in the oral cavity. Cancer Res 64: 5054-5058 https://doi.org/10.1158/0008-5472.CAN-04-1488
  17. Park CB, Fukamachi K, Takasuka N, Han BS, Kim CK, Hamaguchi T. 2004. Rapid induction of skin and mammary tumors in human c-Ha-ras protooncogene travsgenic rats by treatment with 7,12-dimethylbenz[a] anthracene followed by 12-0-tetradecanoylphorbol 13-acetate. Cancer Sci 95: 205-210 https://doi.org/10.1111/j.1349-7006.2004.tb02204.x
  18. Kim SA, Kim YC, Kim SW, Lee SH, Min JJ, Ahn SG, Yoon JH. 2007. Antitumor acivity of novel indirubin derivatives in rat tumor model. Clin Cancer Res 13: 253-239 https://doi.org/10.1158/1078-0432.CCR-06-1154
  19. Carlsson G, Gullberg B, Hafstrom L. 1983. Estimation of liver tumor volume using different formulas-an experimental study in rats. J Cancer Res Clin Oncol 105: 20-23 https://doi.org/10.1007/BF00391826
  20. 한국한의학연구원. 1998. 암예방 및 치료에 의한 한의학적 연구. 한국한의학연구원 연구보고서, 서울. p 2-98
  21. 공현식, 유기원. 1999. 한국한의학의 종양연구에 대한 현황. 제4회 한중학술대회 발표논문집. 서울. p 3-37
  22. 凌一揆. 1999. 中藥本草學. 보건신문사, 서울. p 485-6, 492-6
  23. 신민교. 1997. 임상본초학. 영림사, 서울. p 519-21, 691-2, 731-2
  24. 전국한의과대학 본초학교수 공편. 1998. 본초학. 영림사, 서울. p 413-4, 419-21
  25. Lee KI, Kim SH, Seong RK. 1996. Study on antitumor effect of Salvia miltiorrhiza radix and isolation of active compound. Korean J Oriental Medical Pathology 10: 76-91
  26. Foster KW, Rens S, Louro ID, Lobo-Ruppert SM, Mckie- Bell P, Grizzle W, Hayes MR, Broker TR, Chow LT, Ruppert JM. 1999. Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells: transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF. Cell Growth Differ 10: 423-434
  27. Ruppert JM, Vogelstein B, Kinzler KW. 1991. The zinc finger protein GLI transforms primary cells in cooperation with adenovirus E1A. Mol Cell Biol 11: 1724-1728 https://doi.org/10.1128/MCB.11.3.1724
  28. Torrance CJ, Aqrawal V, Voqelstein B, Kinzler KW. 2001. Use of isogenic human cancer cells for high-throughput screening and drug discovery. Nat Biotechnol 19: 940-945 https://doi.org/10.1038/nbt1001-940
  29. Chapman K, Hall DJ. 2005. Quantifying the activation of the small molecular weight G-protein ras. Biochem Molec Biol Educ 33: 22-27 https://doi.org/10.1002/bmb.2005.494033010420
  30. Kim SA, Kim HW, Kim DG, Lee SG, Park JC, Kang DW, Kim SW, Ahn SG, Yoon JH. 2007. Rapid induction of malignant tumor in Sprague-Dawley rats by injection of RK3E-ras cells. Cancer Lett 235: 53-59 https://doi.org/10.1016/j.canlet.2005.04.003
  31. 서정선. 1998. 20세기말의 의.생물학의 새로운 비전, apoptosis.몸의 효율적 생존을 위한 세포의 능동적 사망기전. 의학연구의 최신동향. 서울. p 30-32