FXYD5 promotes sorafenib resistance through the Akt/mTOR signaling pathway in hepatocellular carcinoma.

Tumor chemoresistance is often a major cause for the failure of chemotherapy. The resistance of hepatocellular carcinoma (HCC) cells to sorafenib significantly limits its therapeutic effect in HCC patients. For the first time, we found that FXYD domain-containing ion transport regulator 5 (FXYD5) is highly expressed in sorafenib-resistant HCC cells. In addition, the protein expression level of FXYD5 was markedly higher in HCC tissues than in paracancerous tissues. Remarkably, downregulation of FXYD5 expression in Huh7/sora cells reversed their resistance to sorafenib. Moreover, overexpression of FXYD5 reduced the sensitivity of HCC cells to sorafenib, while the downregulation of its expression in HCC cells had the opposite effect. We also found abnormal activation of the Akt/mTOR signaling pathway in Huh7/sora cells. Furthermore, MK2206, an Akt inhibitor, was found to significantly increase the sensitivity of HCC cells to sorafenib. More importantly, the expression level of p-Akt was positively correlated with the expression of FXYD5 in HCC tissues. Therefore, mechanistically, FXYD5 enhances the resistance of HCC cells to sorafenib by activating the Akt/mTOR signaling pathway. In conclusion, this study showed that the activation of the FXYD5/Akt/mTOR signaling axis plays key role in the resistance of HCC cells to sorafenib, and FXYD5 may represent a new potential target for HCC therapy.

PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews.

Tree shrew has increasingly become an attractive experimental animal model for human diseases, particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. However, neither normal mammary glands nor breast tumours have been well characterised in the Chinese tree shrew (Tupaia belangeri chinensis). In this study, normal mammary glands from four different developmental stages and 18 spontaneous breast tumours were analysed. Haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) showed that normal mammary gland morphology and structures of tree shrews were quite similar to those found in humans. Spontaneous breast tumours of tree shrews were identified as being intraductal papilloma, papillary carcinoma, and invasive ductal carcinoma with or without lung metastasis. To further analyse breast cancer tumours among tree shrews, 40 3-4 month-old female tree shrews were orally administrated 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil thrice, and then, 15 of these DMBA administrated tree shrews were implanted with medroxyprogesterone acetate (MPA) pellets. DMBA was shown to induce breast tumours (12%) while the addition of MPA increased the tumour incidence (50%). Of these, three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma (IDC). The PTEN/PIK3CA (phosphatase and tensin homologue/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), but not TP53 and GATA3, genes are frequently mutated in breast tumours, and the PTEN/PIK3CA gene mutation status correlated with the expression of pAKT in tree shrew breast tumours. These results suggest that tree shrews may be a promising animal model for a subset of human breast cancers with PTEN/PIK3CA gene mutations.

[Animal models of human glioma: the progress of application and investigation].

The glioma accounts for half of the central nervous tumors, among which the glioblastoma multiforme (GBM) is one of the most aggressive and lethal brain tumors. The difficulties in glioma therapy indicate the need of appropriate animal models for preclinical studies. Benefiting from the development of molecular biology, genetics, and transgenic technology, variable animal models of glioma have been established. These animal models of human glioma are reviewed in this paper.

[Morphological characteristics and cryodamage of Chinese tree shrew (Tupaia belangeri chinensis) sperm].

The tree shrew (Tupaia belangeri chinensis) is a small non-rodent mammal, which is a relatively new experimental animal in medicine due to its close evolutionary relationship to primates and its rapid propagation. Sperm characteristics and cryopreservation in the tree shrew were the main contents of our spermatological research. Epididymal sperm were surgically harvested from male tree shrews captured from the Kunming area. The rate of testis weight to body weight was (1.05±0.07)%, volume of both testis was (1.12 ± 0.10) mL, total sperm from epididymis and vas deferens were 2.2-8.8×10(7), and sperm motility and acrosome integrity were (68.8 ± 3.9)% and (90.0 ± 2.1)%, respectively. Sperm ultrastructure of the tree shrew was examined by scanning electron microscopy and transmission electron microscopy. Tree shrew sperm had a round or oval shaped head of approximately 6.65×5.82 µm, and midpiece, principal piece, tail, and total sperm lengths were 13.39, 52.35, 65.74, and 73.05 µm, respectively. The mitochondria in the midpiece consisted of approximately 48 gyres and had a 9+9+2 axonemal pattern. After freezing and thawing, sperm showed partly intact acrosomes and plasma membrane defects, and sperm breakages, twists, and swellings were found. The tree shrew had similar ultrastructure with other mammalians except for the mitochondria number and the sperm size. Ultrastructural alteration is still the main cause resulting in poor sperm after cryopreservation.