Antitumor Effects of Cistanchis Herba Aqueous Extracts on MCF-7 Human Breast Cancer Cell-Xenograft Athymic Nude Mice, through Potent Immunomodulatory Activities
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목 적: 본 연구의 목적은 유방암 세포(MCF-7) 이식 누드 마우스 모델을 이용하여 육종용 열수 추출물의 면역활성 효과를 통한 항암 활성을 체계적으로 평가하는 것이다. 육종용 열수 추출물은 유방암 치료제로 자주 사용되는 대표적인 경구용 항암제인 tamoxifen 경구 투여군과 비교하여 분석 연구하였다. 방 법: 총 110마리의 6주령 암컷 누드 마우스를 준비하여, 7일간 적응 후 체중이 일정한 마우스를 선정하여 우측 둔부 피하부위에 MCF-7 세포를 이식하였다. 종양세포 이식을 한 지 20일 후, 종양 크기 및 체중을 기준으로 그룹 당 8마리씩 본 실험에 사용하였다. MCF-7 이종 이식 21일 후부터 매일 1회씩 35일간 육종용 열수 추출물을 10 ml/kg의 용량(400, 200 및 100 mg/kg)으로 경구 투여하였으며, tamoxifen 역시 10 ml/kg의 용량(20 mg/kg)으로 경구 투여하였고, 정상 및 종양 이식 매체 대조군에서는 멸균증류수만 종양 이식 21일 후부터 동일한 방법으로 35일간 경구 투여 하였다. 결 과: 본 실험의 결과, MCF-7 세포 이식을 함으로써 현저한 비장 및 하악하 림프절 무게, 혈중 IFN-γ의 함량, IL-1β 및 IL-10의 함량, 비장내 TNF-α, 비장세포 및 복강 대식구의 활성의 감소가 관찰되었고, 비장 및 하악하 림프절의 림프구 감소에 의한 조직병리학적 위축 또한 관찰되었다. 그리고 체중 및 증체량의 감소 역시 관찰되었으며, 혈중 IL-6 함량의 증가, 난소 주위의 지방 무게의 감소 및 조직병리학적으로 난소 주위의 축적 지방 조직 위축 현상이 인정되어, 종양 이식 후에 전형적인 종양과 관련된 면역억제와 악액질 현상이 유발된 것으로 판단되었다. 한편 육종용 열수 추출물 400, 200 및 100 mg/kg 경구 투여군에서는 종양 이식 대조군에 비해 유의성 있는 현저한 항암활성이 투여 용량 의존적으로 관찰되었다. 또한 tamoxifen 20 mg/kg 경구 투여군에서는 종양 관련 악액질 소견이 오히려 악화되는 반면, 육종용 열수 추출물 경구 투여군에서는 면역활성 및 악액질 억제 효과가 관찰되었다. 결 론: 본 연구 결과, 육종용 열수 추출물의 적절한 경구 투여는 심각한 부작용 없이, 종양 관련 악액질 소견을 포함하여, 효과적인 유방암 치료 수단을 제공할 수 있을 것으로 기대된다.
Abstract
Objectives: The purpose of this study is that the anti-tumor, anti-cachexia and immunomodulatory effects of Cistanchis Herba(CH) aqueous extracts were systemically observed in MCF-7 cell xenograft athymic nude mice compared to those of tamoxifen. Methods: 6-week-old 110 female athymic nude mice were prepared, and MCF-7 tumor cells were implanted on the skins of right dorsal hip after 7 days acclimatization. 20 days after tumor inoculation, 8 mice in each group were selected and used in the present study. CH were orally administered in a volume of 10 ㎖/kg, once a day for 35 days from 21 days after tumor cell implantation, as equivalence 400, 200 and 100 mg/kg. Tamoxifen was also orally administered in a volume of 10 ㎖/kg as equivalence 20 mg/kg, in the present experiment. In intact and TB controls, instead of test solutions, only distilled water was also orally administered in a volume of 10 ㎖/kg. Results: As results of tumor cell xenograft in athymic nude mice, great decreases of spleen and submandibular lymph node weights, splenic TNF-α, IL-1β and IL-10 contents, serum IFN-γ, splenic and peritoneal NK cell activities were observed in histopathological atrophic changes of submandibular and spleen lymph nodes. Furthermore, decreases on the body weight and gains were also observed in TB control with increases of serum IL-6 levels, decreases of periovarian fat pad weights, atrophic changes of white adipose tissues, suggesting MCF-7 tumor cell inoculation related immunosuppress and cachexia. Conclusions: The results in this study suggest that appropriate oral administration of CH will provide effective and novel anti-tumor alternative therapeutic regimes, including cancer cachexia control without serious side effects.
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