Ara G, Varshney A, Ha C S, Oseroff A R, Herman T S, Teicher B A
Division of Cancer Pharmacology, Dana Farber Cancer Institute, Boston, MA 02115.
Photochem Photobiol. 1992 Apr;55(4):561-7. doi: 10.1111/j.1751-1097.1992.tb04278.x.
A complex of platinum tetrachloride with two molecules of rhodamine-123 (Rh-123), Pt(Rh-123)2, has been reported to act as hypoxic cell radiosensitizer of carcinoma cells in vitro and in vivo. In the present paper we report that Pt(Rh-123)2 photosensitizes human mammary carcinoma (MCF-7) cells and cis-platinum resistant human mammary carcinoma (MCF-7/CP) cells to 400-800 nm light in vitro. The efficiency of photosensitization by Pt(Rh-123)2 was 10 times greater than for Rh-123. Combination therapy using Pt(Rh-123)2 plus x-ray plus light was also much more effective compared to the combination therapy using Rh-123 plus x-ray plus light. After 15 microM of Rh-123 plus x-ray (0-8 Gy) plus light (5 J/cm2) treatment, cell survival curve was parallel to the x-ray cell survival curve with an initial decrease in the surviving fraction corresponding to the drug plus light mediated killing. Cell killing caused by Rh-123 (15 microM) plus x-ray (0-8 Gy) plus light (5 J/cm2) was additive as determined by the product of the surviving fraction after Rh-123 plus light and x-ray. In contrast, for 15 microM of Pt(Rh-123)2 plus x-ray (8 Gy) plus light (5 J/cm2) treatment, whereas additive killing predicts a survival fraction of approximately 0.024, in reality, the combination therapy caused the survival fraction to decrease to 0.0012, implying that the cell killing was enhanced by a factor of 20. Using Pt(Rh-123)2 plus x-ray plus light, supra-additive cell killing was also observed under hypoxic conditions, although compared to normally oxygenated conditions the degree of cytotoxicity was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
据报道，四氯化铂与两个罗丹明 - 123（Rh - 123）分子形成的配合物Pt(Rh - 123)2在体外和体内可作为癌细胞的乏氧细胞放射增敏剂。在本文中，我们报道了Pt(Rh - 123)2在体外可使人类乳腺癌（MCF - 7）细胞和顺铂耐药的人类乳腺癌（MCF - 7/CP）细胞对400 - 800 nm光产生光致敏作用。Pt(Rh - 123)2的光致敏效率比Rh - 123高10倍。与使用Rh - 123加X射线加光的联合治疗相比，使用Pt(Rh - 123)2加X射线加光的联合治疗也更有效。在15 microM的Rh - 123加X射线（0 - 8 Gy）加光（5 J/cm2）处理后，细胞存活曲线与X射线细胞存活曲线平行，存活分数最初下降对应于药物加光介导的杀伤。由Rh - 123（15 microM）加X射线（0 - 8 Gy）加光（5 J/cm2）引起的细胞杀伤是相加的，这是由Rh - 123加光和X射线后的存活分数乘积确定的。相比之下，对于15 microM的Pt(Rh - 123)2加X射线（8 Gy）加光（5 J/cm2）处理，虽然相加杀伤预测存活分数约为0.024，但实际上联合治疗使存活分数降至0.0012，这意味着细胞杀伤增强了20倍。使用Pt(Rh - 123)2加X射线加光，在乏氧条件下也观察到超相加细胞杀伤，尽管与正常氧合条件相比，细胞毒性程度明显降低。（摘要截短于250字）
