[Effect of resveratrol on PTEN expression and fibrosis of renal tubular epithelial cells in a high-glucose environment].

This study explored the effects of resveratrol(Res) on the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) and the fibrosis of rat renal tubular epithelial cells in a high-glucose environment and the possible mechanism underlying the fibrosis reduction. After the pretreatment of rat renal tubular epithelial cells(NRK-52 E) cultured in a high-glucose condition with Res or PTEN inhibitor SF1670, they were divided into several groups, i.e., normal glucose(NG), normal glucose + SF1670(NS), high glucose(HG), high glucose + SF1670(HS), high glucose + Res at different concentrations(5, 10, 25 µmol·L~(-1)). The expression and distribution of E-cadherin and α-SMA in renal tubular epithelial cells were observed by immunofluorescence cytochemistry. The protein expression levels of PTEN, E-cadherin, α-SMA, p-Akt~((Thr308)) and collagen Ⅳ were determined by Western blot. Real-time PCR was employed to detect the expression of PTEN mRNA. Compared with the NG group, the HG group witnessed the reduced expression of PTEN mRNA, PTEN protein and E-cadherin protein, but saw the increased expression of α-SMA, p-Akt~((Thr308)) and collagen Ⅳ proteins. Besides, with the increase in Res concentration, the expression levels of PTEN mRNA, PTEN protein and E-cadherin protein gradually increased, while those of α-SMA, collagen Ⅳ, p-Akt~((Thr308)) proteins gradually decreased in the Res groups, showing a dose-effect dependence, compared with the HG group. No distinct difference was found between the NS group and the NG group. The expression level of E-cadherin was even lower and those of α-SMA, p-Akt~((Thr308)), and collagen Ⅳ were higher in the HS group than in the HG group, with no marked difference shown in the two groups in terms of PTEN mRNA and protein. Although the PTEN inhibitor did not affect PTEN, the expression changes of the other proteins were opposite to the results after Res treatment and the fibrosis was aggravated, which suggested that SF1670 promoted the fibrosis by inhibiting PTEN, activating Akt and increasing the synthesis of collagen Ⅳ and other extracellular matrix. The results show that Res can antagonize the high glucose-mediated fibrosis of renal tubular epithelial cells. This may be achieved via the up-regulation of PTEN and the inhibition of PI3 K/Akt signaling pathway.

Oncolytic reovirus induces ovarian cancer cell apoptosis in a TLR3-dependent manner.

Globally, ovarian cancer is the seventh most common cancer and the eighth-most common cause of cancer death among women with a five-year survival rate of less than 45%. Although reovirus is known to be effective for treating ovarian cancer, some types of tumor cells still exhibit resistance to reovirus. In order to solve this resistance problem in the treatment of ovarian cancer, we selected the reovirus-resistant OV-90 ovarian cancer cells to study reovirus oncolytic effects. We found that the viability of OV-90 cells decreased after reovirus double-stranded RNA (dsRNA) genome transfection. Interestingly, we observed that chemical blockage of the Toll-like receptor 3 (TLR3)-dsRNA binding complex in OV-90 cells and the inhibition of downstream TLR3 signaling disrupted OV-90 apoptosis triggered by reovirus dsRNA. Together, these results demonstrate that reovirus dsRNA induces reovirus-resistant tumor cell apoptosis through the TLR3 signaling pathway.