背景:尽管我们对大麻素对人体的影响的理解有了很大的进步,他们的许多属性仍然不确定,包括它们潜在的抗肿瘤作用.本研究旨在评估AM1172(一种抑制anandamide细胞摄取的抗水解内源性大麻素类似物)单独给药和与多西他赛(DOCX)联合给药的抗增殖和细胞毒性作用,紫杉醇(PACX),米托蒽醌(MTX)和顺铂(CDDP)对各种人类恶性黑色素瘤A375,FM55P,SK-MEL28和FM55M2细胞系。
方法:在MTT中,LDH,和BrdU检测,当单独给药和与DOCX联合给药时,AM1172的效力和安全性,PACX,MTX,和CDDP确定。
结果:等值线分析显示AM1172与PACX的组合,DOCX,MTX,和CDDP施加累加相互作用,除了在原发性黑色素瘤A375细胞系中AM1172与PACX的组合,观察到协同作用(*p<0.05)。然而,AM1172单独给药时对健康人黑素细胞(HEMA-LP)和人角质形成细胞(HaCaT)产生细胞毒性作用,不幸的是,这限制了其潜在的治疗效用。
结论:AM1172不能单独用作化疗药物,但它可以与PACX结合使用,DOCX,MTX,和CDDP,在各种恶性黑色素瘤细胞系中提供抗增殖作用的累加相互作用。
BACKGROUND: Despite great advances in our understanding of the impact of cannabinoids on human organism, many of their properties still remain undetermined, including their potential antineoplastic effects. This
study was designed to assess the anti-proliferative and cytotoxic effects of AM1172 (a hydrolysis-resistant endocannabinoid analog that inhibits anandamide cellular uptake) administered alone and in combinations with docetaxel (DOCX), paclitaxel (PACX), mitoxantrone (MTX) and cisplatin (CDDP) on various human malignant melanoma A375, FM55P, SK-MEL 28 and FM55M2 cell lines.
METHODS: In the MTT, LDH, and BrdU assays, the potency and safety of AM1172 when administered alone and in combinations with DOCX, PACX, MTX, and CDDP were determined.
RESULTS: The isobolographic analysis revealed that combinations of AM1172 with PACX, DOCX, MTX, and CDDP exerted additive interactions, except for a combination of AM1172 with PACX in primary melanoma A375 cell line, for which synergy was observed (*p<0.05). Nevertheless, AM1172 when administered alone produced cytotoxic effects on healthy human melanocytes (HEMa-LP) and human keratinocytes (HaCaT), which unfortunately limits its potential therapeutic utility.
CONCLUSIONS: AM1172 cannot be used separately as a chemotherapeutic drug, but it can be combined with PACX, DOCX, MTX, and CDDP, offering additive interactions in terms of the anti-proliferative effects in various malignant melanoma cell lines.