Selective anticancer effects of plasma-activated saline in 3D tumor model co-culturing of normal cells and cancer cells

Yujing Xu, Tong Wu, Xixi Jing, Shengduo Xu, Jishen Zhang, Hao Zhang, Dingxin Liu, Li Guo, Han Xu, Xiaohu Wang, Min-Zhi Rong
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Abstract

Compared with conventional 2D cell culture model, the 3D tumor model constructed in vitro is better representative of the tumor microenvironment in vivo. Here, we proposed the utilization of 3D tumor model of co-cultured cancer cells and normal cells to evaluate the selective anticancer effects of cold atmospheric plasma-activated saline (PAS), and expected to provide more precise information about PAS-tumor interactions. By cell sorting, we clarified that A375 melanoma cells and HaCaT normal skin cells purified from the 3D multicellular tumor model differ in sensitivity and responsiveness to PAS compared to the 2D culture model. And during the optimization of PAS treatment parameters, we further found that A375 cells were almost completely killed while HaCaT cells were still present in large numbers after 5 days of certain PAS treatment. Our experiment innovatively carries out the selective study of plasma technology in 3D co-culture system and provides a theoretical basis for further clinical and practical applications of PAS.
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在正常细胞和癌细胞共培养的三维肿瘤模型中,血浆活性生理盐水的选择性抗癌作用
与传统的二维细胞培养模型相比,体外构建的三维肿瘤模型更能代表体内的肿瘤微环境。在此,我们提出利用癌细胞和正常细胞共培养的三维肿瘤模型来评估冷大气等离子体激活生理盐水(PAS)的选择性抗癌作用,并期望提供更精确的 PAS 与肿瘤相互作用的信息。通过细胞分选,我们明确了从三维多细胞肿瘤模型中纯化的 A375 黑色素瘤细胞和 HaCaT 正常皮肤细胞对 PAS 的敏感性和反应性与二维培养模型不同。在优化 PAS 处理参数的过程中,我们进一步发现 A375 细胞几乎被完全杀死,而 HaCaT 细胞在经过一定的 PAS 处理 5 天后仍大量存在。我们的实验创新性地开展了血浆技术在三维共培养系统中的选择性研究,为 PAS 的进一步临床和实际应用提供了理论依据。
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