Inoue S, Hasegawa K, Ito S, Wakamatsu K, Fujita K
School of Health Sciences, Fujita Health University, Aichi, Japan.
Pigment Cell Res. 1993 Oct;6(5):354-8. doi: 10.1111/j.1600-0749.1993.tb00613.x.
The antimalarial agent chloroquine is known for high affinity for melanin. This 4-aminoquinoline derivative was examined for anti-melanoma activity and uptake into melanoma cells. Chloroquine inhibited growth of cultured melanoma cells; the effect was much greater to a moderately pigmented cell line HMV-II than to a nonpigmented HMV-I. Treatment with chloroquine at a dose of 62 mg/kg i.p. for 12 days prolonged by 71% the life span of mice bearing B16 melanoma, while 24-day treatment at 31 mg/kg resulted in a 81% increase in life span. HMV-II cells showed a two-fold increase in uptake of chloroquine as compared with HMV-I cells. Chloroquine, 24 hr after administration to mice implanted s.c. with B16 melanoma, was selectively accumulated in the pigmented tissues, melanoma and eyes. Other nonpigmented tissues such as the liver, lung, and kidney showed rapid uptake (within 1 hr) and release. These results suggest that chloroquine is toxic to pigmented melanoma cells, the process being partly mediated by binding to melanin.
抗疟药氯喹以对黑色素具有高亲和力而闻名。对这种4-氨基喹啉衍生物进行了抗黑色素瘤活性及对黑色素瘤细胞摄取情况的研究。氯喹抑制培养的黑色素瘤细胞生长；对中度色素沉着的细胞系HMV-II的作用比对无色素的HMV-I大得多。以62毫克/千克的剂量腹腔注射氯喹12天，使荷B16黑色素瘤小鼠的寿命延长了71%，而以31毫克/千克的剂量进行24天治疗则使寿命延长了81%。与HMV-I细胞相比，HMV-II细胞对氯喹的摄取增加了两倍。给皮下植入B16黑色素瘤的小鼠注射氯喹24小时后，氯喹选择性地积聚在色素沉着组织、黑色素瘤和眼睛中。其他无色素组织，如肝脏、肺和肾脏，显示出快速摄取（1小时内）和释放。这些结果表明氯喹对色素沉着的黑色素瘤细胞有毒性，这一过程部分是由与黑色素结合介导的。
