Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical Collage, Beijing, China.
Eur J Cancer. 2012 May;48(7):1085-95. doi: 10.1016/j.ejca.2011.06.050. Epub 2011 Jul 20.
Carboxyamidotriazole (CAI) has not only direct anti-cancer activities, but also anti-inflammation effects in a variety of inflammatory animal models. In the present study, we investigated whether macrophages, which are important both in cancer and inflammation, could be regulated by CAI. The results showed that CAI could inhibit tumour necrosis factor-α (TNF-α) production in macrophages in various environments, including those isolated from peritoneal cavity of adjuvant-induced arthritis (AA) rats, from Lewis lung carcinoma (LLC) transplanted tumours and those induced by LLC cells in vitro. Dexamethasone (DEX), one of the pro-inflammatory cytokines inhibitors, could enhance CAI's inhibition of LLC cells proliferation and invasion in macrophages and LLC cells co-culture systems, as well as the tumour growth in vivo. However, DEX failed to enhance CAI's inhibition of LLC cells proliferation when LLC cells were cultured alone, suggesting that the combination of CAI and DEX exerted great anti-tumour effects probably by acting on macrophages in the tumour environment. Over all, we found CAI could act on macrophages and regulate the production of TNF-α not only in inflammatory diseases but also in tumour microenvironment, which might be another anti-tumour mechanism of CAI.
羧基脒三唑（CAI）不仅具有直接的抗癌活性，而且在多种炎症动物模型中具有抗炎作用。在本研究中，我们研究了 CAI 是否可以调节在癌症和炎症中都很重要的巨噬细胞。结果表明，CAI 可以抑制各种环境中巨噬细胞产生肿瘤坏死因子-α（TNF-α），包括从佐剂诱导关节炎（AA）大鼠腹腔分离的巨噬细胞、从 Lewis 肺癌（LLC）移植瘤和体外诱导的巨噬细胞。地塞米松（DEX）是一种促炎细胞因子抑制剂，可增强 CAI 对巨噬细胞和 LLC 细胞共培养系统中 LLC 细胞增殖和侵袭的抑制作用，以及体内肿瘤生长的抑制作用。然而，当 LLC 细胞单独培养时，DEX 未能增强 CAI 对 LLC 细胞增殖的抑制作用，这表明 CAI 和 DEX 的联合作用可能通过作用于肿瘤微环境中的巨噬细胞发挥强大的抗肿瘤作用。总的来说，我们发现 CAI 不仅可以在炎症性疾病中，而且可以在肿瘤微环境中作用于巨噬细胞并调节 TNF-α的产生，这可能是 CAI 的另一种抗肿瘤机制。
