ABSTRACT
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.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of smoking on sperm apoptosis and semen quality of healthy adult males in the main urban area of Chongqing.</p><p><b>METHODS</b>According to the smoking habit, we divided 235 healthy adult males into a non-smoking group (n = 89) and a smoking group (n = 146). Then we detected the routine semen parameters by the computer-assisted semen analysis system and obtained the parameters of sperm apoptosis (the ratios of AN-/PI-, AN+/PI-, AN+/PI+ and AN-/PI+ sperm) by flow cytometry combined with Annexin V-FITC/PI fluorescence staining.</p><p><b>RESULTS</b>The rate of early apoptotic sperm (AN+/PI-) was higher in the smoking than in the non-smoking group ([8.1 +/- 5.1]% vs [6.8 +/- 3.8]%; P = 0.039), but there were no significant differences between the two groups in the rate of late apoptotic sperm (AN+/PI+) ([5.6 +/- 5.2]% vs [5.5 +/- 5.1]%; P = 0.87), as well as in such routine semen indexes as semen volume, sperm density, sperm motility, sperm vitality and normal sperm morphology (P = 0.30, 0.82, 0.37, 0.81 and 0.84, respectively).</p><p><b>CONCLUSION</b>The rate of early apoptotic sperm is higher in smokers than in non-smokers, suggesting that smoking may induce early damage to sperm cells. Compared with routine semen parameters, sperm apoptosis is a more sensitive biomarker to reflect smoking-induced damage to sperm.</p>