Koevary Steven B
Int J Physiol Pathophysiol Pharmacol. 2012;4(2):99-107. Epub 2012 Jun 25.
Rose bengal (RB) has been utilized as a photodynamic agent for the targeted killing of cancer cells. Recent data suggest that intralesional RB alone may be effective in chemoablating locoregional and metastatic melanomas. The ability of RB to induce direct and bystander melanoma cell death led to the speculation that it may be similarly effective in the treatment of other neoplasms. The objective of this study was to determine whether RB can limit the growth, or kill, ovarian cancer cells in vitro. Ovarian carcinoma cells with or without a germline BRCA1 mutation were cultured with up to 800 μM RB for one hour or four days, after which their ability to proliferate was assessed using the MTT assay. Control cells included an embryonic kidney cell line transformed with adenovirus, and normal human fibroblasts. Ovarian cancer cells exhibited significant dose-dependent suppression of growth in response to RB; this suppression was similar to that seen with carboplatin. RB treated ovarian cancer cells appeared rounded, shrunken, and damaged. RB also inhibited the growth of kidney tumor cells but was much less effective in slowing the growth of normal human fibroblasts suggesting that RB-mediated growth suppression might be tumor cell specific. Ovarian cancer cells treated with RB displayed a significant increase in apoptosis that peaked at approximately four times the levels seen in untreated control cells. Furthermore, RB exposure resulted in the intracellular generation of reactive oxygen species (ROS) at levels that were significantly greater than in untreated cells and similar to levels seen in cells treated short term with H(2)O(2). These data suggest that RB may not only suppress ovarian cancer cell growth but also induce their apoptotic cell death, justifying the further investigation of the effects of RB in an animal model of ovarian cancer.
孟加拉玫瑰红(RB)已被用作光动力剂用于靶向杀死癌细胞。最近的数据表明,单独瘤内注射RB可能对局部和转移性黑色素瘤的化学消融有效。RB诱导黑色素瘤细胞直接和旁观者死亡的能力引发了一种推测,即它在治疗其他肿瘤方面可能同样有效。本研究的目的是确定RB在体外是否能限制卵巢癌细胞的生长或杀死卵巢癌细胞。将有或没有种系BRCA1突变的卵巢癌细胞与高达800μM的RB培养1小时或4天,之后使用MTT法评估它们的增殖能力。对照细胞包括用腺病毒转化的胚胎肾细胞系和正常人成纤维细胞。卵巢癌细胞对RB表现出显著的剂量依赖性生长抑制;这种抑制与卡铂所见的相似。经RB处理的卵巢癌细胞显得圆形、萎缩且受损。RB也抑制肾肿瘤细胞的生长,但在减缓正常人成纤维细胞生长方面效果要差得多,这表明RB介导的生长抑制可能是肿瘤细胞特异性的。用RB处理的卵巢癌细胞凋亡显著增加,在大约未处理对照细胞水平的四倍时达到峰值。此外,暴露于RB导致细胞内活性氧(ROS)的产生水平显著高于未处理细胞,且与短期用H₂O₂处理的细胞中所见水平相似。这些数据表明,RB不仅可能抑制卵巢癌细胞生长,还可能诱导其凋亡性细胞死亡,这为进一步研究RB在卵巢癌动物模型中的作用提供了依据。