Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Otolaryngology-Head and Neck Surgery Research Laboratory of Alberta, University of Alberta, Edmonton, Alberta, Canada.
Mol Carcinog. 2019 Nov;58(11):1946-1959. doi: 10.1002/mc.23087. Epub 2019 Jul 24.
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has significantly increased in recent decades due to human papillomavirus (HPV)-mediated oncogenesis. Unfortunately, a growing number of HPV-positive (+) OPSCC survivors are living with the irreversible side effects of treatment. The novel, well-tolerated chemotherapeutics with improved side effect profiles are, therefore, in high demand. Metformin is one such drug, widely used as a first-line oral agent in the treatment of type 2 diabetes mellitus. Curcumin is another well-tolerated agent quickly gaining attention for its medicinal properties. Both metformin and curcumin have been shown to display anticancer properties. This study aimed to determine the antitumor effects of these agents, individually and combined, in HPV+ and HPV-negative (-) head and neck squamous cell carcinoma (HNSCC) cell lines. This was achieved by assessing the efficacy of varying drug concentrations on the overall cell viability, proliferation, and expression of common HNSCC biomarkers. The results from protein and RNA expression data are highly variable, as expected, with multiple pathways being affected in cancer. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and immunofluorescence microscopy suggest that both agents are capable of slowing proliferation and inducing apoptosis. We conclude that curcumin and metformin display effective antitumor effects in both HPV+ and HPV- HNSCC cell lines. The curcumin effects appear more pronounced in the HPV- cell lines. Metformin appears to be more effective at reducing the overall cell numbers in HPV+ cell lines. Metformin and curcumin combined did not appear to have synergistic effects on the proliferation or apoptosis of the treated cell lines.
由于人乳头瘤病毒(HPV)介导的致癌作用,近年来口咽鳞状细胞癌(OPSCC)的发病率显著增加。不幸的是,越来越多的 HPV 阳性(+)OPSCC 幸存者正遭受治疗带来的不可逆转的副作用。因此,人们迫切需要新型、耐受性良好且副作用改善的化疗药物。二甲双胍就是这样一种药物,广泛用作治疗 2 型糖尿病的一线口服药物。姜黄素是另一种耐受性良好的药物,因其药用特性而迅速受到关注。二甲双胍和姜黄素都已显示出抗癌特性。本研究旨在确定这些药物单独和联合使用对 HPV+和 HPV-头颈部鳞状细胞癌(HNSCC)细胞系的抗肿瘤作用。通过评估不同药物浓度对总细胞活力、增殖和常见 HNSCC 生物标志物表达的影响来实现这一目标。蛋白质和 RNA 表达数据的结果高度可变,正如预期的那样,癌症中多个途径受到影响。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐测定法和免疫荧光显微镜检查表明,这两种药物都能够减缓增殖并诱导细胞凋亡。我们得出结论,姜黄素和二甲双胍在 HPV+和 HPV-HNSCC 细胞系中均显示出有效的抗肿瘤作用。姜黄素在 HPV-细胞系中的作用更为明显。二甲双胍似乎在减少 HPV+细胞系中的总细胞数量方面更有效。二甲双胍和姜黄素联合使用对处理过的细胞系的增殖或凋亡似乎没有协同作用。