National Centre of Excellence in Molecular Biology, University of Punjab, 87-West Canal Bank Road, Lahore, Pakistan.
National Centre of Excellence in Molecular Biology, University of Punjab, 87-West Canal Bank Road, Lahore, Pakistan.
Tissue Cell. 2022 Dec;79:101968. doi: 10.1016/j.tice.2022.101968. Epub 2022 Oct 31.
Adipose-derived stem cells (ASCs) have been proven to have tumoricidal effects against hepatic cancer cell lines. However, it appears that exposure to oxidative microenvironment compromises the potential outcome of ASCs in real hepatoma. Herein, we aimed to examine the tumoricidal effects of ASCs under oxidative conditions and to investigate the impact of curcumin priming on ASCs' therapeutic potential.
We used human hepatoma (HepG2) cells in a coculture system with unprimed or curcumin-primed ASCs (Cur-ASCs) under HO-induced oxidative conditions. To investigate HepG2 proliferation and death, MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) and annexin V staining assays were performed. To determine the HepG2 migration and invasion potential, the scratch healing and the transwell invasion assays were performed. To evaluate the expression of apoptosis-protein markers, Western blotting was performed.
Cur-ASCs suppressed HepG2 proliferation, migration, and invasion as well as prompted apoptosis more significantly compared to unprimed ASCs under oxidative conditions. Expressional studies also revealed an obvious decline in the BCL-2/BAX ratio in HepG2 cocultured with Cur-ASCs. In addition, we noticed a marked elevation of apoptosis and senescence in unprimed ASCs compared to Cur-ASCs after coculture experiments, which demonstrated that curcumin priming preserved the survival and growth potential of ASCs; hence, Cur-ASCs performed better tumoricidal functions under oxidative conditions.
Our findings suggest that ASCs have the intrinsic ability to induce cell death in HepG2 cells; however, their functions can be compromised under oxidative conditions. We believe that curcumin priming is an effective approach for improving the therapeutic effectiveness of ASCs in the cancerous microenvironment.
脂肪来源的干细胞（ASCs）已被证明对肝癌细胞系具有杀伤作用。然而，暴露于氧化微环境似乎会影响 ASCs 在真实肝癌中的潜在效果。在此，我们旨在研究 ASCs 在氧化条件下的杀伤作用，并研究姜黄素预培养对 ASCs 治疗潜力的影响。
我们使用人肝癌（HepG2）细胞与未预培养或姜黄素预培养的 ASC（Cur-ASC）在 HO 诱导的氧化条件下进行共培养系统。为了研究 HepG2 的增殖和死亡，进行了 MTT（3-（4,5-二甲基噻唑-2）-2,5-二苯基四唑溴盐）和 Annexin V 染色测定。为了确定 HepG2 的迁移和侵袭潜力，进行了划痕愈合和 Transwell 侵袭测定。为了评估凋亡蛋白标志物的表达，进行了 Western blot 分析。
与未预培养的 ASC 相比，Cur-ASC 在氧化条件下更显著地抑制了 HepG2 的增殖、迁移和侵袭，并促进了凋亡。表达研究还表明，在与 Cur-ASC 共培养的 HepG2 中，BCL-2/BAX 比值明显下降。此外，我们注意到，与 Cur-ASC 相比，共培养实验后未预培养的 ASC 中凋亡和衰老明显增加，这表明姜黄素预培养保留了 ASC 的存活和生长潜力；因此，Cur-ASC 在氧化条件下表现出更好的杀伤功能。
我们的研究结果表明，ASCs 具有内在的诱导 HepG2 细胞死亡的能力；然而，它们的功能可能会在氧化条件下受到影响。我们认为姜黄素预培养是提高 ASCs 在癌症微环境中治疗效果的有效方法。
