Chong Dianlong, Ma Linyan, Liu Fang, Zhang Zhirui, Zhao Surong, Huo Qiang, Zhang Pei, Zheng Hailun, Liu Hao
aBengbu Medical College, Faculty of Pharmacy bDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China.
Anticancer Drugs. 2017 Sep;28(8):831-840. doi: 10.1097/CAD.0000000000000517.
3-Bromopyruvic acid (3-BP) is a well-known inhibitor of energy metabolism. It has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. 5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent for colorectal cancer; however, most patients develop resistance to 5-FU through various mechanisms. The aim of this study was to investigate whether 3-BP has a synergistic antitumor effect with 5-FU on human colorectal cancer cells. In our study, combined 3-BP and 5-FU treatment upregulated p53 and p21, whereas cyclin-dependent kinase CDK4 and CDK2 were downregulated, which led to G0/G1 phase arrest. Furthermore, there was an increase in reactive oxygen species levels and a decrease in adenosine triphosphate levels. It was also observed that Bax expression increased, whereas Bcl-2 expression reduced, which were indicative of mitochondria-dependent apoptosis. In addition, the combination of 3-BP and 5-FU significantly suppressed tumor growth in the BALB/c mice in vivo. Therefore, 3-BP inhibits tumor proliferation and induces S and G2/M phase arrest. It also exerts a synergistic antitumor effect with 5-FU on SW480 cells.
3-溴丙酮酸（3-BP）是一种著名的能量代谢抑制剂。它已被提议作为一种抗癌剂以及与抗癌药物联合使用的化学增敏剂。5-氟尿嘧啶（5-FU）是结直肠癌的一线化疗药物；然而，大多数患者会通过各种机制对5-FU产生耐药性。本研究的目的是探讨3-BP与5-FU对人结肠癌细胞是否具有协同抗肿瘤作用。在我们的研究中，3-BP与5-FU联合处理上调了p53和p21，而细胞周期蛋白依赖性激酶CDK4和CDK2则下调，这导致了G0/G1期阻滞。此外，活性氧水平升高，三磷酸腺苷水平降低。还观察到Bax表达增加，而Bcl-2表达减少，这表明存在线粒体依赖性凋亡。此外，3-BP与5-FU的组合在体内显著抑制了BALB/c小鼠的肿瘤生长。因此，3-BP抑制肿瘤增殖并诱导S期和G2/M期阻滞。它还对SW480细胞与5-FU发挥协同抗肿瘤作用。
