Department of Medical Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing, China.
Department of Pharmacy, Xinqiao Hospital, Chongqing, China.
J Pharm Pharmacol. 2019 Nov;71(11):1684-1694. doi: 10.1111/jphp.13159. Epub 2019 Aug 25.
TNBG-5602 is a newly synthesized compound with an isoquinoline structure. In the present study, we demonstrated the anticancer effect of TNBG-5602 in in-vitro and in-vivo models and investigated its possible anticancer mechanism.
The antiproliferation effect of TNBG-5602 in vitro was evaluated in human liver cancer cell line QGY-7701. The acute toxicity of TNBG-5602 was evaluated in mice. The anticancer activity of TNBG-5602 in vivo was assessed in a xenograft model of human liver cancer cell line QGY-7701.
The results of CCK-8 assay showed that TNBG-5602 can effectively inhibit the proliferation of liver cancer cells in vitro. The acute toxicity test in mice showed that the LD of TNBG-5602 was 172 mg/kg. In a xenograft liver cancer model, TNBG-5602 could remarkably inhibit the growth of tumours. During in-vitro and in-vivo studies, we noted that TNBG-5602 could induce lipid accumulation in cancer cells and tissues. Further study indicated that the anticancer effect of TNBG-5602 may be exerted through activating peroxisome proliferator-activated receptor γ (PPARγ) and downregulating proliferating cell nuclear antigen (PCNA).
Our results suggested that TNBG-5602 might exert potent anticancer activity through increasing the expression of PPARγ.
TNBG-5602 是一种具有异喹啉结构的新合成化合物。本研究旨在体外和体内模型中证实 TNBG-5602 的抗癌作用，并探讨其可能的抗癌机制。
在人肝癌细胞系 QGY-7701 中评估 TNBG-5602 的体外增殖抑制作用。在小鼠中评估 TNBG-5602 的急性毒性。在人肝癌细胞系 QGY-7701 的异种移植模型中评估 TNBG-5602 的体内抗癌活性。
CCK-8 检测结果表明，TNBG-5602 可有效抑制肝癌细胞的体外增殖。小鼠急性毒性试验表明，TNBG-5602 的 LD 为 172mg/kg。在异种移植肝癌模型中，TNBG-5602 可显著抑制肿瘤生长。在体外和体内研究中，我们注意到 TNBG-5602 可诱导癌细胞和组织中的脂质积累。进一步的研究表明，TNBG-5602 的抗癌作用可能是通过激活过氧化物酶体增殖物激活受体 γ（PPARγ）和下调增殖细胞核抗原（PCNA）来实现的。
我们的结果表明，TNBG-5602 可能通过增加 PPARγ 的表达发挥强大的抗癌活性。
