Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition.
Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition.
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大麻素通过抑制 Akt 来减少 ErbB2 驱动的乳腺癌进展。
DOI：
10.1186/1476-4598-9-196
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发表时间：
2010-07-22
期刊：
影响因子：
37.3
通讯作者：
Sanchez, Cristina
中科院分区：
文献类型：
--
作者：
Caffarel, Maria M.;Andradas, Clara;Mira, Emilia;Perez-Gomez, Eduardo;Cerutti, Camilla;Moreno-Bueno, Gema;Flores, Juana M.;Garcia-Real, Isabel;Palacios, Jose;Manes, Santos;Guzman, Manuel;Sanchez, Cristina
ErbB2 阳性乳腺癌的特点是高度侵袭性表型和对标准疗法的反应性降低。尽管已经设计了特定的 ErbB2 靶向疗法，但只有一小部分患者对这些治疗有反应，并且大多数患者最终会复发。这种特别具有攻击性且无反应或复发的患者群体的存在促使人们寻找新的疗法。本研究的目的是确定大麻素是否可能构成治疗 ErbB2 阳性乳腺肿瘤的新治疗工具。我们在 ErbB2 驱动的转移性乳腺癌的成熟且临床相关的模型：MMTV-neu 小鼠中分析了它们的抗肿瘤潜力。我们还分析了一系列 87 个人类乳腺肿瘤中大麻素靶标的表达。我们的结果表明，大麻中最丰富、最有效的大麻素 Δ9-四氢大麻酚和非精神类 CB2 受体选择性激动剂 JWH-133 都能减少 MMTV-neu 小鼠的肿瘤生长、肿瘤数量和肺转移的数量/严重程度。肿瘤的组织学分析表明，大麻素抑制癌细胞增殖，诱导癌细胞凋亡，并损害肿瘤血管生成。大麻素的抗肿瘤作用至少部分依赖于对促肿瘤 Akt 通路的抑制。我们还发现 91% 的 ErbB2 阳性肿瘤表达非精神药物大麻素受体 CB2。总而言之，这些结果为使用基于大麻素的疗法治疗 ErbB2 阳性乳腺癌提供了强有力的临床前证据。
ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.
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影响因子：
11.2
作者：
Blazquez, Cristina;Salazar, Maria;Guzman, Manuel
通讯作者：
Guzman, Manuel
影响因子：
8
作者：
Caffarel, M. M.;Moreno-Bueno, G.;Sanchez, C.
通讯作者：
Sanchez, C.
影响因子：
3.5
作者：
Laezza, Chlara;Pisanti, Simona;Bifulco, Maurizio
通讯作者：
Bifulco, Maurizio
影响因子：
3.5
作者：
Melck, D;Rueda, D;Di Marzo, V
通讯作者：
Di Marzo, V
影响因子：
11.2
作者：
Caffarel, Maria M.;Sarrio, David;Sanchez, Cristina
通讯作者：
Sanchez, Cristina