School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529020, PR China.
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China.
Eur J Pharmacol. 2021 Feb 15;893:173840. doi: 10.1016/j.ejphar.2020.173840. Epub 2020 Dec 24.
Cancer stem cell (CSC) plays an important role in pancreatic cancer pathogenesis and treatment failure. CSCs are characterized by their ability to form tumor spheres in serum-free medium and expression of CSC related markers. In the present study, we investigated the effect atorvastatin, celecoxib and tipifarnib in combination on proliferation and apoptosis in Panc-1 sphere-forming cells. The sphere-forming cells were isolated from Panc-1 cells by sphere-forming method. These sphere-forming cells showed CSC properties. The levels of CD44, CD133 and ALDH1A1 in the sphere-forming cells were increased. Moreover, Panc-1 sphere-forming cells were resistant to chemotherapeutic drug gemcitabine. Combined atorvastatin with celecoxib and tipifarnib synergistically decreased the sphere forming ability of Panc-1 cells and the drug combination also strongly inhibited cell proliferation and promoted apoptosis in the sphere-forming cells. The effects of the drug combination on the Panc-1 sphere-forming cells were associated with decreases in the levels of CD44, CD133 and ALDH1A1, and suppression of Akt and NF-κB activation. Results of the present study indicate that the combination of atorvastatin, celecoxib and tipifarnib may represent an effective approach for inhibiting pancreatic CSCs.
癌症干细胞 (CSC) 在胰腺癌的发病机制和治疗失败中起着重要作用。CSC 的特征是能够在无血清培养基中形成肿瘤球体，并表达 CSC 相关标志物。在本研究中，我们研究了阿托伐他汀、塞来昔布和替匹法尼联合应用对 Panc-1 球体形成细胞增殖和凋亡的影响。球体形成细胞通过球体形成方法从 Panc-1 细胞中分离出来。这些球体形成细胞表现出 CSC 特性。CD44、CD133 和 ALDH1A1 在球体形成细胞中的水平增加。此外，Panc-1 球体形成细胞对化疗药物吉西他滨具有耐药性。阿托伐他汀与塞来昔布和替匹法尼联合使用可协同降低 Panc-1 细胞的球体形成能力，且药物联合使用还可强烈抑制球体形成细胞的增殖并促进其凋亡。药物联合使用对 Panc-1 球体形成细胞的作用与 CD44、CD133 和 ALDH1A1 水平的降低以及 Akt 和 NF-κB 激活的抑制有关。本研究结果表明，阿托伐他汀、塞来昔布和替匹法尼的联合应用可能代表抑制胰腺 CSC 的有效方法。
