McClay E F, Winski P J, Jones J A, Jennerette J, Gattoni-Celli S
Department of Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston 20403, USA.
Cancer Res. 1996 Sep 1;56(17):3866-9.
We have been investigating the synergistic cytotoxic interactions between tamoxifen (TAM) and cisplatin (DDP) in human malignant cell lines. Recent data have demonstrated that TAM activates phospholipase D, which can increase the production of prostaglandin D2. Prostaglandin D2 has been shown to have growth inhibitory properties in several malignant cell lines. delta 12-Prostaglandin-J2 (delta 12-PG J2) is a derivative of prostaglandin D2 that has been shown to have similar inhibitory properties. We hypothesized that TAM may increase the production of delta 12-PG J2, which in turn may synergize with DDP. To begin our investigation of this interaction, we sought to determine if delta 12-PG J2 was cytotoxic and synergistic in our melanoma system and then expanded our observations to include a wide range of malignant cells. We have demonstrated that delta 12-PG J2 is cytotoxic to multiple malignant cell lines including melanoma, ovarian, prostate, colon, pancreas, small cell lung cancer, and breast cancer lines. The IC50s ranged from 0.70 microM (small cell lung cancer) to 3.30 microM (DDP-resistant melanoma). Additionally, delta 12-PG J2 exhibited synergistic cytotoxicity with both DDP and ionizing radiation. These data suggest that delta 12-PG J2 should be further evaluated in an in vivo model to confirm activity.
我们一直在研究他莫昔芬（TAM）和顺铂（DDP）在人恶性细胞系中的协同细胞毒性相互作用。最近的数据表明，TAM可激活磷脂酶D，从而增加前列腺素D2的产生。前列腺素D2已被证明在几种恶性细胞系中具有生长抑制特性。δ12-前列腺素-J2（δ12-PG J2）是前列腺素D2的一种衍生物，已被证明具有类似的抑制特性。我们假设TAM可能会增加δ12-PG J2的产生，而δ12-PG J2反过来可能与DDP产生协同作用。为了开始对这种相互作用的研究，我们试图确定δ12-PG J2在我们的黑色素瘤系统中是否具有细胞毒性和协同作用，然后将我们的观察扩展到包括多种恶性细胞。我们已经证明，δ12-PG J2对多种恶性细胞系具有细胞毒性，包括黑色素瘤、卵巢癌、前列腺癌、结肠癌、胰腺癌、小细胞肺癌和乳腺癌细胞系。IC50范围从0.70微摩尔（小细胞肺癌）到3.30微摩尔（顺铂耐药黑色素瘤）。此外，δ12-PG J2与DDP和电离辐射均表现出协同细胞毒性。这些数据表明，δ12-PG J2应在体内模型中进一步评估以确认其活性。
