Kerr Candace, Adhikary Gautam, Grun Daniel, George Nicholas, Eckert Richard L
Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland.
Department of Dermatology, The University of Maryland School of Medicine, Baltimore, Maryland.
Mol Carcinog. 2018 Jan;57(1):3-11. doi: 10.1002/mc.22714. Epub 2017 Aug 28.
Epidermal squamous cell carcinoma is an extremely common type of cancer. Early tumors can be successfully treated by surgery, but recurrent disease is aggressive and resistant to therapy. Cisplatin is often used as a treatment, but the outcome is rarely satisfactory. For this reason new strategies are required. Sulforaphane is a diet-derived cancer prevention agent that is effective in suppressing tumor growth in animal models of skin cancer. We monitored the efficacy of sulforaphane and cisplatin as a combined therapy for squamous cell carcinoma. Both agents suppress cell proliferation, growth of cancer stem cell spheroids, matrigel invasion and migration of SCC-13 and HaCaT cells, and combination treatment is more efficient. In addition, SCC-13 cell derived cancer stem cells are more responsive to these agents than non-stem cancer cells. Both agents suppress tumor formation, but enhanced suppression is observed with combined treatment. Moreover, both agents reduce the number of tumor-resident cancer stem cells. SFN treatment of cultured cells or tumors increases apoptosis and p21 level, and both agents increase tumor apoptosis. We suggest that combined therapy with sulforaphane and cisplatin is efficient in suppressing tumor formation and may be a treatment option for advanced epidermal squamous cell carcinoma.
表皮鳞状细胞癌是一种极为常见的癌症类型。早期肿瘤可通过手术成功治疗,但复发性疾病具有侵袭性且对治疗有抗性。顺铂常被用作一种治疗手段,但其效果很少令人满意。因此,需要新的策略。萝卜硫素是一种源自饮食的癌症预防剂,在皮肤癌动物模型中能有效抑制肿瘤生长。我们监测了萝卜硫素和顺铂联合治疗鳞状细胞癌的疗效。两种药物都能抑制细胞增殖、癌干细胞球的生长、基质胶侵袭以及SCC - 13和HaCaT细胞的迁移,联合治疗更为有效。此外,SCC - 13细胞衍生的癌干细胞比非干细胞癌细胞对这些药物更敏感。两种药物都能抑制肿瘤形成,但联合治疗时抑制作用增强。而且,两种药物都能减少肿瘤中驻留的癌干细胞数量。用萝卜硫素处理培养细胞或肿瘤会增加细胞凋亡和p21水平,两种药物都会增加肿瘤细胞凋亡。我们认为,萝卜硫素和顺铂联合治疗在抑制肿瘤形成方面是有效的,可能是晚期表皮鳞状细胞癌的一种治疗选择。