RÉSUMÉ
Hepatocellular carcinoma (HCC) is a common malignant tumor worldwise. The incidence rate of HCC is high and is easy to metastasis and recurrence, which seriously affects human health. Traditional chemical drugs have some challenges such as toxicity, side effects, and multidrug resistance, thus it is urgent to find new drugs and effective targets. Here we synthesized a novel chemical, protonic bis-phenanthroline (H-BP), and the antitumor effect was investigated in the study. The results showed that H-BP could selectively inhibit the proliferation of tumor cells and cause HCC apoptosis. And also, in HCC tumor-bearing mice, H-BP could effectively prevent the growth of tumor mass, even completely eliminate the tumor at medium dose (5 mg·kg-1) and high dose (10 mg·kg-1), and meanwhile H-BP has no significant effect on the body weight of mice. The experimental protocol was approved by the Animal Ethics Committee of Southwest University, and the experimental operation was strictly carried out in accordance with the ethical principles of animal use and care. Mechanism studies showed that H-BP induced HCC apoptosis was related to down-regulation the expression of pleomorphic adenoma gene like-2 (PLAGL2), a oncogene transcription factor, resulting in the down-regulation of PLAGL2 downstream proteins hypoxia inducible factor and β-catenin. This study not only introduces the dimerization method to form novel compounds that will provide a new approach for drug design, but also suggests that PLAGL2 may be an effective target in tumor therapy.
RÉSUMÉ
Objective To investigate the effect of short hairpin RNA(shRNA)-mediated pleomorphic adenoma gene like-2 (PALAG2) silencing on the malignant behavior of hepatocellular carcinoma cells and its mechanism. Methods Real-time PCR and Western blotting were used to detect the expression level of PLAGL2 in liver cancer tissues and adjacent tissues. Hepatoma cells MHCC97-L were cultured in vitro, the lentiviral vector plasmid PLAGL2-shRNA and control NC-shRNA were constructed, transfected into MHCC97-L cells, and stable transfected strains were selected with puromycin. CCK-8 and Transwell chamber assay detected the proliferation activity and the number of migration and invasion of MHCC97-L cells after silencing PLAGL2. Western blotting was used to detect the expression of p-PI3K and p-Akt proteins. The PI3K/ Akt signaling pathway activator was used to treat MHCC97-L cells to detect cell proliferation, migration and invasion. Results The expression of PLAGL2 was significantly increased in liver cancer tissue (P < 0. 05). Transfection of 9 strains of MHCC97-L cells with PLAGL2-shRNA could significantly reduce the expression level of PLAGL2, and the ability of proliferation, migration, and invasion of MHCC97-L cells was also weakened (P<0. 05), and the expression levels of p-PI3K, and p-Akt were inhibited (P<0. 05), PI3K/ Akt activator could obviously reverse the above phenomenon. Conclusion shRNA lentiviral vector pathway can effectively silence the expression of PLAGL2 gene in hepatocarcinoma cells. Silencing of PLAGL2 can significantly inhibit the malignant behavior of proliferation, migration and invasion of hepatocarcinoma cells, and its mechanism may be related to the inhibition of PI3K / Akt signaling pathway activation.