Ma Wantong, Zhang Qianqian, Li Xue, Ma Yunhao, Liu Yuheng, Hu Shujian, Zhou Zhongkun, Zhang Rentao, Du Kangjia, Syed Ashikujaman, Yao Xiaojun, Chen Peng
School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
College of Chemistry and Chemical Engineering, Lanzhou University, 222 Tianshui South Road, Lanzhou, 730000, PR China.
Eur J Pharm Sci. 2020 Sep 1;152:105464. doi: 10.1016/j.ejps.2020.105464. Epub 2020 Jul 12.
Colorectal cancer (CRC), a major health threat in the world, ranks third in incidence and second in mortality among cancers. Chemotherapy, an important treatment for colorectal cancer, have be limited in the clinic due to the resistance and side effect. Studies have shown that PI3K-related regulatory pathways play a colossal role in colorectal cancer. Therefore, it is a good strategy to find a new drug which works by affecting the PI3K signaling pathway. In this paper, we obtained a new vanillin derivative (IPM712) by modifying the structure of IPM711 and tested its anticancer activity in vitro and toxicity in vivo. Results showed that IPM712 has a better anticancer activity than 5-Fu in HCT116 and SW480 cell lines. Furthermore, IPM712 can inhibit cell proliferation, migration and induce the apoptosis by affecting PI3K-related protein expression. Acute toxicity experiments show that IPM712 has no significant toxicity at therapeutic concentrations. Based on these results, IPM712 is a promising anticancer drug candidate for human colorectal cancer therapy.
结直肠癌(CRC)是全球主要的健康威胁,其发病率在癌症中排名第三,死亡率排名第二。化疗是结直肠癌的重要治疗方法,但由于耐药性和副作用,在临床上受到限制。研究表明,PI3K相关调控通路在结直肠癌中起着巨大作用。因此,寻找一种通过影响PI3K信号通路发挥作用的新药是一个很好的策略。在本文中,我们通过修饰IPM711的结构获得了一种新的香草醛衍生物(IPM712),并在体外测试了其抗癌活性,在体内测试了其毒性。结果表明,在HCT116和SW480细胞系中,IPM712比5-氟尿嘧啶具有更好的抗癌活性。此外,IPM712可通过影响PI3K相关蛋白表达抑制细胞增殖、迁移并诱导细胞凋亡。急性毒性实验表明,IPM712在治疗浓度下无明显毒性。基于这些结果,IPM712是一种有前途的用于人类结直肠癌治疗的抗癌药物候选物。