암 대사 치료 / 의학전문 논문 사이트 pubmed 에 게재돤 삼중 음성 유방암 진행을 막는 디피리다몰

 

암 대사 치료 / 의학전문 논문 사이트 pubmed 에 게재돤 삼중 음성 유방암 진행을 막는 디피리다몰

 

디피리다몰은 허혈성 질환에서 널리 처방되는 약물이며 유방암의 새로운 치료법으로 잠재적인 임상 용도로 조사 받고있다. 삼중 음성 유방암 4T1-Luc 또는 MDA-MB-231T 세포를 가진 이종이식 생쥐를 만들었다.

 

이러한 in vivo 모델에서, dipyridamole 효과는 일차 종양 성장, 전이 형성, 세포주기, 세포 사멸, 신호 전달 경로, 면역 세포 침윤 및 혈청 염증성 사이토 카인 수준을 조사했다. 디피리다몰은 복강내 투여에 의해 원발성 종양의 성장과 전이 형성을 유의하게 감소시켰다.

 

15 mg/kg/day dipyridamole을 처리한 결과, 1차 종양의 평균 크기가 67.5% 감소하였고(p = 0.0433), 30 mg/kg/day dipyridamole을 처리한 결과 1차 종양의 평균 크기가 거의 감소하였다(p = 0.0182). 실험 전이 분석 결과,

 

디피리다몰은 MDA-MB-231T 이종이식모델에서 47.5% 감소하였고(p = 0.0122), 4T1-Luc 이종이식모델에서 50.26% 감소하였다(p = 0.0292). in vivo dipyridamole은 β-catenin의 활성을 38.64 % (p < 0.0001), phospho-ERK1/2를 25.05 % (p = 0.0129), phospho-p65를 67.82 % (p < 0.0001) 감소시켰으며, IkBα의 발현을 두 배로 증가시켜 Wnt, ERK1/2-MA에 유의한 영향을 주었다.

 

두 동물 모델에서 PK와 NF-kB 경로가 모두 나타났다. 또한, 디피리다몰은 원발성 종양에서 종양과 관련된 대식세포와 골수유래 억제세포의 침윤을 유의하게 감소시켰으며(p<0.05), 치료된 마우스의 혈청에서 염증성 사이토카인의 수치를 감소시켰다. 적절한 용량과 정확한 투여 방식으로 사용될 때, 디피리다몰은 유방암 치료에 유망한 물질이며, 따라서 높은 활성화된 경로를 보여주는 다른 암에서의 잠재적인 사용을 암시한다.

 

디피리다몰 [Dipyridamolum] : 협심증 치료와 뇌졸중 예방에 쓰이는 의약품

[약학] 협심증 치료와 뇌졸중 예방에 쓰이는 의약품. 혈관 확장과 혈소판 응집 억제 작용을 한다

 

근거자료  https://www.ncbi.nlm.nih.gov/pubmed/22760522

 

2013 Jan;30(1):47-68. doi: 10.1007/s10585-012-9506-0. Epub 2012 Jul 4.

 

Dipyridamole prevents triple-negative breast-cancer progression.

Spano D1, Marshall JC, Marino N, De Martino D, Romano A, Scoppettuolo MN, Bello AM, Di Dato V, Navas L, De Vita G, Medaglia C, Steeg PS, Zollo M.

Author information

1Centro di Ingegneria Genetica Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy.

 

Abstract

Dipyridamole is a widely prescribed drug in ischemic disorders, and it is here investigated for potential clinical use as a new treatment for breast cancer. Xenograft mice bearing triple-negative breast cancer 4T1-Luc or MDA-MB-231T cells were generated. In these in vivo models, dipyridamole effects were investigated for primary tumor growth, metastasis formation, cell cycle, apoptosis, signaling pathways, immune cell infiltration, and serum inflammatory cytokines levels. Dipyridamole significantly reduced primary tumor growth and metastasis formation by intraperitoneal administration. Treatment with 15 mg/kg/day dipyridamole reduced mean primary tumor size by 67.5 % (p = 0.0433), while treatment with 30 mg/kg/day dipyridamole resulted in an almost a total reduction in primary tumors (p = 0.0182). Experimental metastasis assays show dipyridamole reduces metastasis formation by 47.5 % in the MDA-MB-231T xenograft model (p = 0.0122), and by 50.26 % in the 4T1-Luc xenograft model (p = 0.0292). In vivo dipyridamole decreased activated β-catenin by 38.64 % (p < 0.0001), phospho-ERK1/2 by 25.05 % (p = 0.0129), phospho-p65 by 67.82 % (p < 0.0001) and doubled the ｅxpression of IkBα (p = 0.0019), thus revealing significant effects on Wnt, ERK1/2-MAPK and NF-kB pathways in both animal models. Moreover dipyridamole significantly decreased the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in primary tumors (p < 0.005), and the inflammatory cytokines levels in the sera of the treated mice. We suggest that when used at appropriate doses and with the correct mode of administration, dipyridamole is a promising agent for breast-cancer treatment, thus also implying its potential use in other cancers that show those highly activated pathways.