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
Alterations of mitochondrial structure and function in tumor cells allow cell survival and proliferation under hypoxic and acidic microenvironment. The effect of normal mitochondria on tumor initiation and development remains unknown. In this study, mice were euthanized by rapid cervical dislocation for isolation of hepatic mitochondria, which were injected intravenously to melanoma-bearing mice. This animal experiment had been approved by Southwest University Experiment Animal Ethics Review Committee. The results showed that exogenous mitochondria can significantly inhibit the growth of melanoma. Mitochondria isolated from the liver of young mice had more potent anti-melanoma effect than those isolated from aging mice. The average volume of tumors decreased significantly from 1.35 cm3 to 0.34 cm3, and the average mass of tumors decreased significantly from 0.63 g to 0.22 g. This anti-tumor mechanism might be associated with induction of mitophagy and cell necrosis after the exogenous mitochondria entering the melanoma cells. As mitotherapy can clinically improve somatic cell survival for treatment of pediatric patients with myocardial ischemia, the observed anti-tumor effect of exogenous mitochondria provides a hope for selective tumor treatment.
ABSTRACT
Mitochondria is an important organelle in mammalian cells with multiple functions,such as ener-gy production and cell homeostasis maintaining. It is known that hundreds of diseases are associated with mi-tochondrial defects. The studies show that the exoge-nous mitochondria can directly enter mammalian cells in vitro, and they also can quickly transform into ani-mal tissues by local or intravenous injection. Current-ly, it has raised a new therapeutic strategy for mito-chondrial diseases, called mitotherapy, which trans-plants exogenous functional mitochondria into mito-chondria-defective cells. The mitochondria in recipient cells play their own roles, including energy produc-tion,maintaining free radical balance,and cell viabili-ty recovery. Since there is no effective method for mito-chondria-related diseases up to now, the mitotherapy will provide a new approach for the prevention and treatment of these diseases.
ABSTRACT
Blood-brain barrier (BBB) is the major obstacle for drug delivery into the central nervous system (CNS). However, there is no ideal model animal for the study of BBB permeability till now. Currently zebrafish (Danio rerio) has emerged as a powerful model organism for the study of vertebrate biology. In this study, the feasibility of using zebrafish as model animal was investigated for BBB permeability by comparing the results of administration of BBB-penetrating peptide and protein to mouse and zebrafish. The results showed that the BBBs of mouse and zebrafish were similar in molecular permeability. Additionally, zebrafish has advantageous features as a model animal, such as small size, fertile and easy to breed. Therefore, it is suggested that zebrafish may be a favored model for the study of BBB permeability.