Wigington D P, Urben C M, Strugnell S A, Knutson J C
Bone Care International, 1600Aspen Commons, Middleton, WI 53562, USA.
Anticancer Res. 2004 Sep-Oct;24(5A):2905-12.
Vitamin D compounds are important modulators of cellular proliferation and differentiation, with potential utility as anticancer drugs. 1,24(S)-Dihydroxyvitamin D2 [1,24(OH)2D2] is a naturally occurring active vitamin D compound with low calcemic activity.
We evaluated the growth inhibitory effects of 1,24(OH)2D2 on LNCaP prostate cancer and MCF-7 breast cancer cells. 1,24(OH)2D2 was evaluated alone and in paired combination with nine chemotherapeutic agents. Drug interactions were analyzed using the median-effect/isobologram method. Combination index values were used to characterize the interactions as synergistic, additive, or antagonistic.
In MCF-7 cells, 1,24(OH)2D2 produced synergistic effects with doxonrubicin and cisplatin and additive effects with busulfan, etoposide, tamaxifen, 5-fluorouracil and carboplatin. In LNCaP cells, 1,24(OH)2D2 produced a synergistic effect with carboplatin and additive effects with doxorubicin, busulfan, paclitaxel and etoposide.
We conclude that 1,24(OH)2D2 may have therapeutic value in the treatment of prostate and breast cancers, alone or in combination with chemotherapeutic agents.
维生素D化合物是细胞增殖和分化的重要调节剂，具有作为抗癌药物的潜在效用。1,24(S)-二羟基维生素D2[1,24(OH)2D2]是一种天然存在的活性维生素D化合物，具有低血钙活性。
我们评估了1,24(OH)2D2对LNCaP前列腺癌细胞和MCF-7乳腺癌细胞的生长抑制作用。单独评估了1,24(OH)2D2，并将其与九种化疗药物配对联合使用。使用中位效应/等效线图法分析药物相互作用。联合指数值用于将相互作用表征为协同、相加或拮抗。
在MCF-7细胞中，1,24(OH)2D2与多柔比星和顺铂产生协同作用，与白消安、依托泊苷、他莫昔芬、5-氟尿嘧啶和卡铂产生相加作用。在LNCaP细胞中，1,24(OH)2D2与卡铂产生协同作用，与多柔比星、白消安、紫杉醇和依托泊苷产生相加作用。
我们得出结论，1,24(OH)2D2单独或与化疗药物联合使用可能对前列腺癌和乳腺癌的治疗具有治疗价值。
