Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veteran General Hospital, Taipei, Taiwan, R.O.C.
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
Oncol Rep. 2018 Feb;39(2):651-658. doi: 10.3892/or.2017.6126. Epub 2017 Dec 1.
Autologous fat grafting procedures have noted a markedly increased frequency, not only for cosmetic purposes, but also for deformities after head and neck cancer and breast cancer surgery. Carcinogenesis is always a major concern in cell therapy-related issues. However, there is no literature discussing this issue in head and neck squamous cell carcinoma patients. To evaluate the interaction of tongue cancer cells and adipose-derived stem cells, we performed a series of in vitro experiments. Our results demonstrated that cisplatin significantly reduced the viabilities of SCC‑25 and CAL‑27 cells in a concentration-dependent manner, but it had low cytotoxicity in cisplatin-resistant CAL‑27 (CAR) cells. There was no significant difference in terms of viability among the SCC‑25, CAL‑27, and CAR cells in the adipose-derived stem cell conditioned medium and control groups. There was also no significant difference in terms of cell migration as determined by wound healing assay of SCC‑25, CAL‑27, and CAR cells between the adipose-derived stem cell conditioned medium treatment and control treatment. Importantly, the adipose-derived stem cell conditioned medium attenuated cisplatin-triggered cell death in the SCC‑25 and CAL‑27 cells. Moreover, adipose-derived stem cell conditioned medium markedly inhibited cisplatin-induced apoptotic cell death (sub‑G1 phase) in the CAL‑27 cells. Western blot analyses indicated that cisplatin-induced reductions in pro‑caspase‑3, pro‑caspase‑9, phospho-BAD, phospho-IGF-1R, phospho-AKT, and phospho-ERK in CAL‑27 cells were reversed by adipose-derived stem cell conditioned medium supplement. Taken together, we provide evidence that adipose-derived stem cell conditioned medium protects CAL‑27 cells from cisplatin-induced cell death, possibly through upregulation of the IGF-1R/AKT/ERK signaling pathway.
自体脂肪移植术的应用频率显著增高,不仅可用于美容目的,还可用于头颈部癌症和乳腺癌手术后的畸形矫正。细胞治疗相关问题一直存在致癌风险。然而,目前尚无文献讨论头颈部鳞状细胞癌患者的这一问题。为了评估舌癌细胞与脂肪来源干细胞的相互作用,我们进行了一系列体外实验。我们的结果表明,顺铂以浓度依赖性方式显著降低 SCC-25 和 CAL-27 细胞的活力,但对顺铂耐药的 CAL-27(CAR)细胞的细胞毒性较低。在脂肪来源干细胞条件培养基和对照组中,SCC-25、CAL-27 和 CAR 细胞的活力无显著差异。划痕愈合试验也表明,脂肪来源干细胞条件培养基处理组和对照组 SCC-25、CAL-27 和 CAR 细胞的迁移能力无显著差异。重要的是,脂肪来源干细胞条件培养基可减轻 SCC-25 和 CAL-27 细胞中顺铂引发的细胞死亡。此外,脂肪来源干细胞条件培养基可显著抑制 CAL-27 细胞中顺铂诱导的凋亡性细胞死亡(亚 G1 期)。Western blot 分析表明,脂肪来源干细胞条件培养基可逆转顺铂诱导的 CAL-27 细胞中 pro-caspase-3、pro-caspase-9、磷酸化 BAD、磷酸化 IGF-1R、磷酸化 AKT 和磷酸化 ERK 的减少。综上所述,我们提供的证据表明,脂肪来源干细胞条件培养基可保护 CAL-27 细胞免受顺铂诱导的细胞死亡,这可能是通过上调 IGF-1R/AKT/ERK 信号通路实现的。