Liao Tian, Wei Wen-Jun, Wen Duo, Hu Jia-Qian, Wang Yu, Ma Ben, Cao Yi-Min, Xiang Jun, Guan Qing, Chen Jia-Ying, Sun Guo-Hua, Zhu Yong-Xue, Li Duan-Shu, Ji Qing-Hai
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
J Cancer. 2018 Mar 29;9(8):1329-1336. doi: 10.7150/jca.21915. eCollection 2018.
Verteporfin, a FDA approved second-generation photosensitizer, has been demonstrated to have anticancer activity in various tumors, but not including papillary thyroid cancer (PTC). In current pre-clinical pilot study, we investigate the effect of verteporfin on proliferation, apoptosis, cell cycle and tumor growth of PTC. Our results indicate verteporfin attenuates cell proliferation, arrests cell cycle in G2/S phase and induces apoptosis of PTC cells. Moreover, treatment of verteporfin dramatically suppresses tumor growth from PTC cells in xenograft mouse model. We further illustrate that exposure to MEK inhibitor U0126 inactivates phosphorylation of ERK1/2 and MEK in verteporfin-treated PTC cells. These data suggest verteporfin exhibits inhibitory effect on PTC cells proliferation and cell cycle partially via ERK1/2 signalling pathway, which strongly encourages the further application of verteporfin in the treatment against PTC.
维替泊芬是一种经美国食品药品监督管理局(FDA)批准的第二代光敏剂,已被证明在多种肿瘤中具有抗癌活性,但不包括甲状腺乳头状癌(PTC)。在当前的临床前初步研究中,我们研究了维替泊芬对PTC细胞增殖、凋亡、细胞周期和肿瘤生长的影响。我们的结果表明,维替泊芬可减弱细胞增殖,使细胞周期停滞于G2/S期,并诱导PTC细胞凋亡。此外,在异种移植小鼠模型中,维替泊芬治疗可显著抑制PTC细胞的肿瘤生长。我们进一步证明,在维替泊芬处理的PTC细胞中,暴露于MEK抑制剂U0126可使ERK1/2和MEK的磷酸化失活。这些数据表明,维替泊芬部分通过ERK1/2信号通路对PTC细胞增殖和细胞周期发挥抑制作用,这有力地推动了维替泊芬在PTC治疗中的进一步应用。