UniSA STEM, University of South Australia, Adelaide, SA 5095, Australia.
College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Int J Mol Sci. 2022 Jul 10;23(14):7631. doi: 10.3390/ijms23147631.
Seven different inhibitors of the heme metabolic pathway were applied in combination with HAL to study the formation of PpIX in bladder cancer HT1197 and normal fibroblast HFFF2 cells ex vivo, specifically with the aim to increase the fluorescence contrast between cancer and non-cancer cells. The mRNA expression of enzymes involved in the heme biosynthesis pathway were measured via PCR following incubation with the drugs in order to link the fluorescence levels and metabolic activity. The exogenous administration of HAL does lead to cancer-specific PpIX accumulation. However, the contrast between cancer and normal cells in suspension was not enhanced by the enzyme inhibitors and iron-chelating agents tested, nor did the mRNA expression necessarily correlate with the fluorescence intensity. The results indicate that a difference in the metabolic activity of cells in suspension may limit the applicability of exogenous enzyme inhibitor administration as a mean to improve the fluorescence-based detection of cancer cells shed in body fluids.
七种不同的血红素代谢途径抑制剂与 HAL 联合应用于膀胱癌 HT1197 和正常成纤维细胞 HFFF2 细胞的体外研究，旨在增加癌细胞和非癌细胞之间的荧光对比。用药物孵育后，通过 PCR 测量参与血红素生物合成途径的酶的 mRNA 表达，以将荧光水平与代谢活性联系起来。外源性 HAL 的给药确实导致了癌症特异性 PpIX 的积累。然而，在所测试的酶抑制剂和铁螯合剂中，悬浮细胞之间的荧光对比并没有增强，mRNA 表达也不一定与荧光强度相关。结果表明，悬浮细胞代谢活性的差异可能限制了外源性酶抑制剂给药作为提高体液中脱落癌细胞荧光检测的适用性。
